Vaccines

2024

Jump to: 2023, 2022, 2021

18 pages, 3309 KiB

Open AccessArticle

CT584 Is Not a Protective Vaccine Antigen against Respiratory Chlamydial Challenge in Mice

by Steven Hoang-Phou, Sukumar Pal, Anatoli Slepenkin, Abisola Abisoye-Ogunniyun, Yuliang Zhang, Sean F. Gilmore, Megan L. Shelby, Feliza A. Bourguet, Mariam V. Mohagheghi, Aleksandr Noy, Amy Rasley, Luis M. de la Maza and Matthew A. Coleman

Vaccines 2024, 12(10), 1134; https://doi.org/10.3390/vaccines12101134 - 3 Oct 2024

Viewed by 625

Abstract

Background:Chlamydia trachomatis is the most prevalent bacterial sexually transmitted pathogen in humans worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein [...] Read more.

Background:Chlamydia trachomatis is the most prevalent bacterial sexually transmitted pathogen in humans worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein synthesis (CFPS) utilizes the cellular protein manufacturing machinery decoupled from the requirement for maintaining cellular viability, offering the potential for flexible, rapid, and decentralized production of recombinant protein vaccine antigens. Methods: Here, we use CFPS to produce the full-length putative chlamydial type three secretion system (T3SS) needle-tip protein, CT584, for evaluation as a vaccine antigen in mouse models. High-speed atomic force microscopy (HS-AFM) (RIBM, Tsukuba, Japan) imaging and computer simulations confirm that CFPS-produced CT584 retains a native-like structure prior to immunization. Female mice were primed with CT584 adjuvanted with CpG-1826 intranasally (i.n.) or CpG-1826 + Montanide ISA 720 intramuscularly (i.m.), followed four weeks later by an i.m. boost before respiratory challenge with 10⁴ inclusion forming units (IFU) of Chlamydia muridarum. Results: Immunization with CT584 generated robust antibody responses but weak cell-mediated immunity and failed to protect against i.n. challenge as demonstrated by body weight loss, increased lung weights, and the presence of high numbers of IFUs in the lungs. Conclusion: While CT584 was not a protective vaccine candidate, the speed and flexibility with which CFPS can be used to produce other potential chlamydial antigens make it an attractive technique for antigen production. Full article

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17 pages, 2419 KiB

Open AccessArticle

Mtb-Specific HLA-E-Restricted T Cells Are Induced during Mtb Infection but Not after BCG Administration in Non-Human Primates and Humans

by Linda Voogd, Marjolein van Wolfswinkel, Iman Satti, Andrew D. White, Karin Dijkman, Anele Gela, Krista E. van Meijgaarden, Kees L. M. C. Franken, Julia L. Marshall, Tom H. M. Ottenhoff, Thomas J. Scriba, Helen McShane, Sally A. Sharpe, Frank A. W. Verreck and Simone A. Joosten

Vaccines 2024, 12(10), 1129; https://doi.org/10.3390/vaccines12101129 - 1 Oct 2024

Viewed by 941

Abstract

Background: Novel vaccines targeting the world’s deadliest pathogen Mycobacterium tuberculosis (Mtb) are urgently needed as the efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted Mtb [...] Read more.

Background: Novel vaccines targeting the world’s deadliest pathogen Mycobacterium tuberculosis (Mtb) are urgently needed as the efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted Mtb-specific CD8⁺ T cells can control intracellular Mtb growth, making HLA-E a promising vaccine target for Mtb. Methods: In this study, we evaluated the frequency and phenotype of HLA-E-restricted Mtb-specific CD4⁺/CD8⁺ T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. Results: BCG vaccination followed by Mtb challenge in NHPs did not affect the frequency of circulating and local HLA-E–Mtb CD4⁺ and CD8⁺ T cells, and we saw the same in humans receiving BCG. HLA-E–Mtb T cell frequencies were significantly increased after Mtb challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Conclusions: Together, HLA-E–Mtb-restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after Mtb infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB. Full article

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10 pages, 2007 KiB

Open AccessBrief Report

Immunogenicity Analysis of Chikungunya Virus DNA Vaccine Based on Mutated Putative N-Linked Glycosylation Sites of the Envelope Protein

by Kwangwook Kim, Seo Young Moon, Seungyeon Kim, In-Ohk Ouh, Yookyoung Lee and Heeji Lim

Vaccines 2024, 12(10), 1097; https://doi.org/10.3390/vaccines12101097 - 26 Sep 2024

Viewed by 615

Abstract

Chikungunya fever is a mosquito-borne infectious disease caused by the chikungunya virus (CHIKV). Recently, CHIKV has spread rapidly worldwide, raising global concerns. However, there is only one approved vaccine is available to prevent CHIKV infection; therefore, different platform vaccines development is a public [...] Read more.

Chikungunya fever is a mosquito-borne infectious disease caused by the chikungunya virus (CHIKV). Recently, CHIKV has spread rapidly worldwide, raising global concerns. However, there is only one approved vaccine is available to prevent CHIKV infection; therefore, different platform vaccines development is a public health priority. The CHIKV genome encodes four non-structural polyproteins (nsP1-4) and one structural polyprotein (capsid, envelope 3, envelope 2, 6 K, and envelope 1). Previous studies have shown that N-linked glycans in viral proteins play important roles in regulating immune responses. Accordingly, in this study, we designed four CHIKV DNA vaccine candidates with mutated N-glycosylation sites in the full-length E and E I/II proteins. Our results indicated that immunization of mice with the vaccine elevated the cytokines levels, including IFN-γ, associated with T cell immune response. Furthermore, the truncated E protein with a deleted E III domain (E I/II) exhibited better immunogenicity than the full-length E protein, and N-linked glycosylation of E I/II protein induced a higher cell-mediated immune response. Overall, our study demonstrates that N-linked glycosylation of the E I/II proteins of CHIKV significantly enhances cell-mediated immune responses, laying the foundation for the development of potential vaccination strategies against CHIKV. Full article

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15 pages, 880 KiB

Open AccessArticle

Population Movement and Poliovirus Spread across Pakistan and Afghanistan in 2023

by Irshad Ali Sodhar, Jaishri Mehraj, Anum S. Hussaini, Muhammad Aamir, Jahanuddin Mahsaud, Shabbir Ahmed, Ahmed Ali Shaikh, Asif Ali Zardari, Shumaila Rasool, Shoukat Ali Chandio and Erin M. Stuckey

Vaccines 2024, 12(9), 1006; https://doi.org/10.3390/vaccines12091006 - 1 Sep 2024

Viewed by 1873

Abstract

Population movement dynamics are a critical part of understanding communicable disease transmission patterns and determining where, when, and with whom to deliver appropriate prevention interventions. This study aimed to identify the origin of the Afghan population and their patterns of movement within Karachi, [...] Read more.

Population movement dynamics are a critical part of understanding communicable disease transmission patterns and determining where, when, and with whom to deliver appropriate prevention interventions. This study aimed to identify the origin of the Afghan population and their patterns of movement within Karachi, to assess the polio vaccination status of children under the age of five, and to investigate the travel history and guest arrival patterns of individuals from Afghanistan and other regions known to be affected by wild poliovirus type 1 (WPV1) within the past six months. A cross-sectional survey was conducted in selected 12 union councils of Karachi, Pakistan. The data were collected through interviews with Afghan household members and from the frontline workers (FLWs) responsible for the polio vaccination of the children of the same households. Cohen’s kappa was used to check the agreement between information provided by the household participant and FLWs. A total of 409 Afghan household members were interviewed. Travel of any household member outside the city within the last six months was reported by 105 (25.7%) participants, 140 (34.2%) hosted guests within the last six months, and 92 (22.5%) participants reported that guest children were vaccinated in their households. A total of 230 (56.2%) participants observed polio teams at relatives’ households within Karachi, and 127 (31.1%) observed polio teams at relatives’ households outside Karachi in different districts of Pakistan and Afghanistan. Fair to moderate agreement was observed between information provided by the household members and FLWs on the variable’s duration of living at current residence (Kappa = 0.370), travel history (Kappa = 0.429), guest arrival (Kappa = 0.395), and household children vaccinated for OPV (Kappa = 0.419). Substantial population mobility was observed between Afghanistan and Pakistan as well as significant movement of the Afghan population within Karachi in the last six months. These findings warrant attention and targeted implementation of interventions to enhance and sustain both routine and supplementary immunization activities within this demographic group. Full article

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15 pages, 2656 KiB

Open AccessArticle

Trichinella spiralis Infection Inhibits the Efficacy of RBD Protein of SARS-CoV-2 Vaccination via Regulating Humoral and Cellular Immunity

by Feifan Zhu, Wenwen Zheng, Yiyan Gong, Jinyuan Zhang, Yihan Yu, Jixian Zhang, Mengjun Liu, Fei Guan and Jiahui Lei

Vaccines 2024, 12(7), 729; https://doi.org/10.3390/vaccines12070729 - 30 Jun 2024

Viewed by 1235

Abstract

Vaccines are the most effective and feasible way to control pathogen infection. Helminths have been reported to jeopardize the protective immunity mounted by several vaccines. However, there are no experimental data about the effect of helminth infection on the effectiveness of COVID-19 vaccines. [...] Read more.

Vaccines are the most effective and feasible way to control pathogen infection. Helminths have been reported to jeopardize the protective immunity mounted by several vaccines. However, there are no experimental data about the effect of helminth infection on the effectiveness of COVID-19 vaccines. Here, a mouse model of trichinosis, a common zoonotic disease worldwide, was used to investigate effects of Trichinella spiralis infection on the RBD protein vaccine of SARS-CoV-2 and the related immunological mechanism, as well as the impact of albendazole (ALB) deworming on the inhibitory effect of the parasite on the vaccination. The results indicated that both the enteric and muscular stages of T. spiralis infection inhibited the vaccine efficacy, evidenced by decreased levels of IgG, IgM, sIgA, and reduced serum neutralizing antibodies, along with suppressed splenic germinal center (GC) B cells in the vaccinated mice. Pre-exposure to trichinosis promoted Th2 and/or Treg immune responses in the immunized mice. Furthermore, ALB treatment could partially reverse the inhibitory effect of T. spiralis infection on the efficiency of the vaccination, accompanied by a restored proportion of splenic GC B cells. Therefore, given the widespread prevalence of helminth infections worldwide, deworming therapy needs to be considered when implementing COVID-19 vaccination strategies. Full article

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17 pages, 2593 KiB

Open AccessArticle

Using Surface Immunogenic Protein as a Carrier Protein to Elicit Protective Antibody to Multiple Serotypes for Candidate Group B Streptococcal Glycan Conjugate Vaccines

by Huiqi Duan, Wenhua Huang, Qingyu Lv, Peng Liu, Qian Li, Decong Kong, Xuyang Sun, Xinran Zhang, Yongqiang Jiang and Shaolong Chen

Vaccines 2024, 12(6), 573; https://doi.org/10.3390/vaccines12060573 - 24 May 2024

Viewed by 1096

Abstract

Group B Streptococcus (GBS) is a life-threatening opportunistic pathogen, particularly in pregnant women, infants, and the elderly. Currently, maternal vaccination is considered the most viable long-term option for preventing GBS mother-to-infant infection, and two polysaccharide conjugate vaccines utilizing CRM197 as a carrier protein [...] Read more.

Group B Streptococcus (GBS) is a life-threatening opportunistic pathogen, particularly in pregnant women, infants, and the elderly. Currently, maternal vaccination is considered the most viable long-term option for preventing GBS mother-to-infant infection, and two polysaccharide conjugate vaccines utilizing CRM197 as a carrier protein have undergone clinical phase II trials. Surface immunogenic protein (Sip), present in all identified serotypes of GBS strains so far, is a protective surface protein of GBS. In this study, the type Ia capsular polysaccharide (CPS) of GBS was utilized as a model to develop candidate antigens for a polysaccharide conjugate vaccine by coupling it with the Sip of GBS and the traditional carrier protein CRM197. Serum analysis from immunized New Zealand rabbits and CD1 mice revealed that there was no significant difference in antibody titers between the Ia-Sip group and Ia-CRM197 group; however, both were significantly higher than those observed in the Ia polysaccharide group. Opsonophagocytosis and passive immune protection results using rabbit serum indicated no significant difference between the Ia-Sip and Ia-CRM197 groups, both outperforming the Ia polysaccharide group. Furthermore, serum from the Ia-Sip group had a cross-protective effect on multiple types of GBS strains. The challenge test results in CD1 mice demonstrated that the Ia-Sip group provided complete protection against lethal doses of bacteria and also showed cross-protection against type III strain. Our study demonstrates for the first time that Ia-Sip is immunogenic and provides serotype-independent protection in glycan conjugate vaccines, which also indicates Sip may serve as an excellent carrier protein for GBS glycan conjugate vaccines and provide cross-protection against multiple GBS strains. Full article

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2023

Jump to: 2024, 2022, 2021

24 pages, 1552 KiB

Open AccessReview

Outer Membrane Vesicles from Acinetobacter baumannii: Biogenesis, Functions, and Vaccine Application

by Zheqi Weng, Ning Yang, Shujun Shi, Zining Xu, Zixu Chen, Chen Liang, Xiuwei Zhang and Xingran Du

Vaccines 2024, 12(1), 49; https://doi.org/10.3390/vaccines12010049 - 31 Dec 2023

Cited by 5 | Viewed by 2277

Abstract

This review focuses on Acinetobacter baumannii, a Gram-negative bacterium that causes various infections and whose multidrug resistance has become a significant challenge in clinical practices. There are multiple bacterial mechanisms in A. baumannii that participate in bacterial colonization and immune responses. It [...] Read more.

This review focuses on Acinetobacter baumannii, a Gram-negative bacterium that causes various infections and whose multidrug resistance has become a significant challenge in clinical practices. There are multiple bacterial mechanisms in A. baumannii that participate in bacterial colonization and immune responses. It is believed that outer membrane vesicles (OMVs) budding from the bacteria play a significant role in mediating bacterial survival and the subsequent attack against the host. Most OMVs originate from the bacterial membranes and molecules are enveloped in them. Elements similar to the pathogen endow OMVs with robust virulence, which provides a new direction for exploring the pathogenicity of A. baumannii and its therapeutic pathways. Although extensive research has been carried out on the feasibility of OMV-based vaccines against pathogens, no study has yet summarized the bioactive elements, biological activity, and vaccine applicability of A. baumannii OMVs. This review summarizes the components, biogenesis, and function of OMVs that contribute to their potential as vaccine candidates and the preparation methods and future directions for their development. Full article

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10 pages, 2667 KiB

Open AccessArticle

Impact of Varicella Immunization and Public Health and Social Measures on Varicella Incidence: Insights from Surveillance Data in Shanghai, 2013–2022

by Liming Shi, Jia Lu, Xiaodong Sun, Zhi Li, Liping Zhang, Yihan Lu and Ye Yao

Vaccines 2023, 11(11), 1674; https://doi.org/10.3390/vaccines11111674 - 1 Nov 2023

Cited by 1 | Viewed by 1429

Abstract

To evaluate the impact of a two-dose VarV program on varicella incidence among the whole population, considering the influence of public health and social measures (PHSMs), we extracted surveillance data on varicella cases during 2013–2022 in Minhang, Shanghai. Then, we estimated the incidence [...] Read more.

To evaluate the impact of a two-dose VarV program on varicella incidence among the whole population, considering the influence of public health and social measures (PHSMs), we extracted surveillance data on varicella cases during 2013–2022 in Minhang, Shanghai. Then, we estimated the incidence trend of varicella through interrupted time-series analyses and quantified the impact of the immunization program and PHSMs using Serfling regression. We also explored the associations between PHSMs and varicella cases. The implementation of the two-dose VarV strategy was followed by a significant decrease in varicella incidence (−1.84% per month). After one year of the program, varicella incidence was estimated at a 45.25% reduction, which was higher in children (59.12% and 54.09%) than in adults (19.49%). The decrease attributed to PHSMs was 31.26% during 2020–2022, and school closing was identified as the most relevant PHSM (b = −8.03 cases, r = −0.67 with a 1-week lag). These findings indicate that the two-dose immunization program has more effectively reduced the varicella incidence compared with the one-dose vaccine, and interventions like school closings are also encouraged to serve as supplementary measures to prevent varicella epidemics. Full article

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17 pages, 2190 KiB

Open AccessArticle

Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes

by Peter A. Barry, Smita S. Iyer and Laura Gibson

Vaccines 2023, 11(11), 1629; https://doi.org/10.3390/vaccines11111629 - 24 Oct 2023

Cited by 1 | Viewed by 1526

Abstract

HCMV vaccine development has traditionally focused on viral antigens identified as key targets of neutralizing antibody (NAb) and/or T cell responses in healthy adults with chronic HCMV infection, such as glycoprotein B (gB), the glycoprotein H-anchored pentamer complex (PC), and the unique long [...] Read more.

HCMV vaccine development has traditionally focused on viral antigens identified as key targets of neutralizing antibody (NAb) and/or T cell responses in healthy adults with chronic HCMV infection, such as glycoprotein B (gB), the glycoprotein H-anchored pentamer complex (PC), and the unique long 83 (UL83)-encoded phosphoprotein 65 (pp65). However, the protracted absence of a licensed HCMV vaccine that reduces the risk of infection in pregnancy regardless of serostatus warrants a systematic reassessment of assumptions informing vaccine design. To illustrate this imperative, we considered the hypothesis that HCMV proteins infrequently detected as targets of T cell responses may contain important vaccine antigens. Using an extant dataset from a T cell profiling study, we tested whether HCMV proteins recognized by only a small minority of participants encompass any T cell epitopes. Our analyses demonstrate a prominent skewing of T cell responses away from most viral proteins—although they contain robust predicted CD8 T cell epitopes—in favor of a more restricted set of proteins. Our findings raise the possibility that HCMV may benefit from evading the T cell recognition of certain key proteins and that, contrary to current vaccine design approaches, including them as vaccine antigens could effectively take advantage of this vulnerability. Full article

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10 pages, 685 KiB

Open AccessCommunication

Evaluation of Cross-Immunity to the Mpox Virus Due to Historic Smallpox Vaccination

by Giulia Matusali, Elisa Petruccioli, Eleonora Cimini, Francesca Colavita, Aurora Bettini, Eleonora Tartaglia, Settimia Sbarra, Silvia Meschi, Daniele Lapa, Massimo Francalancia, Licia Bordi, Valentina Mazzotta, Sabrina Coen, Klizia Mizzoni, Alessia Beccacece, Emanuele Nicastri, Luca Pierelli, Andrea Antinori, Enrico Girardi, Francesco Vaia, Alessandro Sette, Alba Grifoni, Delia Goletti, Vincenzo Puro and Fabrizio Maggi Show full author list Hide full author list

Vaccines 2023, 11(10), 1541; https://doi.org/10.3390/vaccines11101541 - 28 Sep 2023

Cited by 7 | Viewed by 1689

Abstract

When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples (n = 97) and PBMCs (n = [...] Read more.

When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples (n = 97) and PBMCs (n = 30) from healthy-donors, either born before 1974 and reporting smallpox vaccination during childhood or born after 1975 and not vaccinated with Vaccinia virus (VACV)-based vaccines. We evaluated the levels of anti-MPXV IgG and neutralizing antibodies (Nabs) and the presence of a T cell response against MPXV. We found anti-MPXV IgG and Nabs in 60 (89.6%) and 40 (70.1%) vaccinated individuals, respectively. We observed a T cell response to Orthopoxviruses and MPXV peptide pools in 30% of vaccinated individuals. We thus show that a high proportion of subjects who received the smallpox vaccine 40 to 60 years ago have humoral cross-immunity, while the T-cell-specific response against MPXV was observed in a smaller group (30%) of vaccinated individuals. This study, combined with information on immunity developed during natural infection or the administration of current vaccines, will contribute to a better understanding of humoral and cellular responses against MPXV. Full article

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15 pages, 3344 KiB

Open AccessArticle

Comparative Transcriptome Profiling of mRNA and lncRNA of Mouse Spleens Inoculated with the Group ACYW135 Meningococcal Polysaccharide Vaccine

by Nan Zhu, Liping Hu, Wenlong Hu, Qiang Li, Haiguang Mao, Mengting Wang, Zhijian Ke, Lili Qi and Jinbo Wang

Vaccines 2023, 11(8), 1295; https://doi.org/10.3390/vaccines11081295 - 28 Jul 2023

Viewed by 1367

Abstract

The Group ACYW135 meningococcal polysaccharide vaccine (MPV-ACYW135) is a classical common vaccine used to prevent Neisseria meningitidis serogroups A, C, Y, and W135, but studies on the vaccine at the transcriptional level are still limited. In the present study, mRNAs and lncRNAs related [...] Read more.

The Group ACYW135 meningococcal polysaccharide vaccine (MPV-ACYW135) is a classical common vaccine used to prevent Neisseria meningitidis serogroups A, C, Y, and W135, but studies on the vaccine at the transcriptional level are still limited. In the present study, mRNAs and lncRNAs related to immunity were screened from the spleens of mice inoculated with MPV-ACYW135 and compared with the control group to identify differentially expressed mRNAs and lncRNAs in the immune response. The result revealed 34375 lncRNAs and 41321 mRNAs, including 405 differentially expressed (DE) lncRNAs and 52 DE mRNAs between the MPV group and the control group. Results of GO and KEGG enrichment analysis turned out that the main pathways related to the immunity of target genes of those DE mRNAs and DE lncRNAs were largely associated with positive regulation of T cell activation, CD8-positive immunoglobulin production in mucosal tissue, alpha-beta T cell proliferation, negative regulation of CD4-positive, and negative regulation of interleukin-17 production, suggesting that the antigens of MPV-ACYW135 capsular polysaccharide might activate T cell related immune reaction in the vaccine inoculation. In addition, it was noted that Bach2 (BTB and CNC homolog 2), the target gene of lncRNA MSTRG.17645, was involved in the regulation of immune response in MPV-ACYW135 vaccination. This study provided a preliminary catalog of both mRNAs and lncRNAs associated with the proliferation and differentiation of body immune cells, which was worthy of further research to enhance the understanding of the biological immune process regulated by MPV-ACYW135. Full article

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14 pages, 1886 KiB

Open AccessArticle

Estimating the Cost-Effectiveness of Switching to Higher-Valency Pediatric Pneumococcal Conjugate Vaccines in the United Kingdom

by Michele Wilson, Aaron Lucas, Diana Mendes, Andrew Vyse, Boglarka Mikudina, Carole Czudek, Gillian Frances Ellsbury and Johnna Perdrizet

Vaccines 2023, 11(7), 1168; https://doi.org/10.3390/vaccines11071168 - 28 Jun 2023

Cited by 6 | Viewed by 2448

Abstract

Currently, the 13-valent pneumococcal conjugate vaccine (PCV13) is administered under a 1+1 (1 primary dose) pediatric schedule in the United Kingdom (UK). Higher-valency PCVs, 15-valent PCV (PCV15), or 20-valent PCV (PCV20) might be considered to expand serotype coverage. We evaluated the cost-effectiveness of [...] Read more.

Currently, the 13-valent pneumococcal conjugate vaccine (PCV13) is administered under a 1+1 (1 primary dose) pediatric schedule in the United Kingdom (UK). Higher-valency PCVs, 15-valent PCV (PCV15), or 20-valent PCV (PCV20) might be considered to expand serotype coverage. We evaluated the cost-effectiveness of PCV20 or PCV15 using either a 2+1 (2 primary doses) or 1+1 schedule for pediatric immunization in the UK. Using a dynamic transmission model, we simulated future disease incidence and costs under PCV13 1+1, PCV20 2+1, PCV20 1+1, PCV15 2+1, and PCV15 1+1 schedules from the UK National Health Service perspective. We prospectively estimated disease cases, direct costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Scenario analyses were performed to estimate the impact of model assumptions and parameter uncertainty. Over a five-year period, PCV20 2+1 averted the most disease cases and gained the most additional QALYs. PCV20 2+1 and 1+1 were dominant (cost-saving and more QALYs gained) compared with PCV15 (2+1 or 1+1) and PCV13 1+1. PCV20 2+1 was cost-effective (GBP 8110/QALY) compared with PCV20 1+1. PCV20 was found cost-saving compared with PCV13 1+1, and PCV20 2+1 was cost-effective compared with PCV20 1+1. Policymakers should consider the reduction in disease cases with PCV20, which may offset vaccination costs. Full article

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26 pages, 1943 KiB

Open AccessArticle

A Data-Driven Approach to Construct a Molecular Map of Trypanosoma cruzi to Identify Drugs and Vaccine Targets

by Swarsat Kaushik Nath, Preeti Pankajakshan, Trapti Sharma, Priya Kumari, Sweety Shinde, Nikita Garg, Kartavya Mathur, Nevidita Arambam, Divyank Harjani, Manpriya Raj, Garwit Kwatra, Sayantan Venkatesh, Alakto Choudhoury, Saima Bano, Prashansa Tayal, Mahek Sharan, Ruchika Arora, Ulrich Strych, Peter J. Hotez, Maria Elena Bottazzi and Kamal Rawal Show full author list Hide full author list

Vaccines 2023, 11(2), 267; https://doi.org/10.3390/vaccines11020267 - 26 Jan 2023

Cited by 2 | Viewed by 4613

Abstract

Chagas disease (CD) is endemic in large parts of Central and South America, as well as in Texas and the southern regions of the United States. Successful parasites, such as the causative agent of CD, Trypanosoma cruzi have adapted to specific hosts during [...] Read more.

Chagas disease (CD) is endemic in large parts of Central and South America, as well as in Texas and the southern regions of the United States. Successful parasites, such as the causative agent of CD, Trypanosoma cruzi have adapted to specific hosts during their phylogenesis. In this work, we have assembled an interactive network of the complex relations that occur between molecules within T. cruzi. An expert curation strategy was combined with a text-mining approach to screen 10,234 full-length research articles and over 200,000 abstracts relevant to T. cruzi. We obtained a scale-free network consisting of 1055 nodes and 874 edges, and composed of 838 proteins, 43 genes, 20 complexes, 9 RNAs, 36 simple molecules, 81 phenotypes, and 37 known pharmaceuticals. Further, we deployed an automated docking pipeline to conduct large-scale docking studies involving several thousand drugs and potential targets to identify network-based binding propensities. These experiments have revealed that the existing FDA-approved drugs benznidazole (Bz) and nifurtimox (Nf) show comparatively high binding energies to the T. cruzi network proteins (e.g., PIF1 helicase-like protein, trans-sialidase), when compared with control datasets consisting of proteins from other pathogens. We envisage this work to be of value to those interested in finding new vaccines for CD, as well as drugs against the T. cruzi parasite. Full article

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10 pages, 277 KiB

Open AccessReview

COVID-19, SARS-CoV-2 Vaccination, and Human Herpesviruses Infections

by Peter A. C. Maple

Vaccines 2023, 11(2), 232; https://doi.org/10.3390/vaccines11020232 - 20 Jan 2023

Cited by 7 | Viewed by 4226

Abstract

There are several human herpesviruses. A common characteristic of infection by these viruses is latency, by which the virus assumes a non-replicative state, subverting the attentions of the host’s immune response. In immunocompetent hosts, herpesviruses are immunologically controlled, although periodic virus shedding can [...] Read more.

There are several human herpesviruses. A common characteristic of infection by these viruses is latency, by which the virus assumes a non-replicative state, subverting the attentions of the host’s immune response. In immunocompetent hosts, herpesviruses are immunologically controlled, although periodic virus shedding can occur. In situations where immunological control is lost, herpesviruses can reactivate and produce clinically apparent disease. It is now becoming apparent that COVID-19 or exposure to COVID-19 vaccines can exert several effects on the immune system. The pandemic of COVID-19 shows no sign of abating, with new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants continuing to evolve. Several COVID-19 vaccines have been developed, and much of the world’s population has either experienced COVID-19 or been vaccinated against it. There are an increasing number of reports of associations between herpesvirus infections or reactivations and COVID-19 or COVID-19 vaccination. For instance, a positive cytomegalovirus serostatus may indicate a greater likelihood of severe COVID-19, and herpes simplex virus reactivation may be linked to increased mortality. Epstein–Barr virus reactivation appears to be associated with post-acute sequelae of COVID-19. Finally, herpes zoster has been reported to be associated with COVID-19 vaccination. This brief narrative review will provide several insights into associations between herpesvirus infections or reactivations and COVID-19 or SARS-CoV-2 vaccination. Full article

2022

Jump to: 2024, 2023, 2021

5 pages, 444 KiB

Open AccessCase Report

Vaccine-Associated Rubella Caused by the RA 27/3 Strain

by Manuel Paz, Magaly Padilla, Eduardo Perez, Jessica Sauceda and Adrian Camacho

Vaccines 2023, 11(1), 65; https://doi.org/10.3390/vaccines11010065 - 28 Dec 2022

Cited by 1 | Viewed by 2093

Abstract

Vaccine-associated rubella is a very rare adverse effect after rubella vaccination; we report the characteristics of a young women who, after a vaccination campaign where she received three different vaccines against influenza, tetanus/diphtheria, and measles/rubella, developed a fever and rash consistent with rubella [...] Read more.

Vaccine-associated rubella is a very rare adverse effect after rubella vaccination; we report the characteristics of a young women who, after a vaccination campaign where she received three different vaccines against influenza, tetanus/diphtheria, and measles/rubella, developed a fever and rash consistent with rubella disease that was confirmed by sequencing of the virus. The evolution was favorable. The woman had two close contacts who did not develop the disease. Follow-up of the patient and her contacts was important to detect complications and for epidemiology surveillance. Full article

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17 pages, 1703 KiB

Open AccessArticle

Molecular Lipopolysaccharide Di-Vaccine Protects from Shiga-Toxin Producing Epidemic Strains of Escherichia coli O157:H7 and O104:H4

by Ivan A. Dyatlov, Edward A. Svetoch, Anna A. Mironenko, Boris V. Eruslanov, Victoria V. Firstova, Nadezhda K. Fursova, Alexander L. Kovalchuk, Vyacheslav L. Lvov and Petr G. Aparin

Vaccines 2022, 10(11), 1854; https://doi.org/10.3390/vaccines10111854 - 1 Nov 2022

Cited by 2 | Viewed by 1863

Abstract

Background: Shiga toxin-producing Escherichia coli (STEC) O157:H7 and O104:H4 strains are important causative agents of food-borne diseases such as hemorrhagic colitis and hemolytic–uremic syndrome, which is the leading cause of kidney failure and death in children under 5 years as well as in [...] Read more.

Background: Shiga toxin-producing Escherichia coli (STEC) O157:H7 and O104:H4 strains are important causative agents of food-borne diseases such as hemorrhagic colitis and hemolytic–uremic syndrome, which is the leading cause of kidney failure and death in children under 5 years as well as in the elderly. Methods: the native E. coli O157:H7 and O104:H4 lipopolysaccharides (LPS) were partially deacylated under alkaline conditions to obtain apyrogenic S-LPS with domination of tri-acylated lipid A species—Ac₃-S-LPS. Results: intraperitoneal immunization of BALB/c mice with Ac₃-S-LPS antigens from E. coli O157:H7 and O104:H4 or combination thereof (di-vaccine) at single doses ranging from 25 to 250 µg induced high titers of serum O-specific IgG (mainly IgG1), protected animals against intraperitoneal challenge with lethal doses of homologous STEC strains (60–100% survival rate) and reduced the E. coli O157:H7 and O104:H4 intestinal colonization under an in vivo murine model (6–8-fold for monovalent Ac₃-S-LPS and 10-fold for di-vaccine). Conclusions: Di-vaccine induced both systemic and intestinal anti-colonization immunity in mice simultaneously against two highly virulent human STEC strains. The possibility of creating a multivalent STEC vaccine based on safe Ac₃-S-LPS seems to be especially promising due to a vast serotype diversity of pathogenic E. coli. Full article

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11 pages, 887 KiB

Open AccessArticle

Measles Virus Neutralizing Antibody Response and Durability Two Years after One or Two Doses of Measles–Mumps–Rubella Vaccine among Young Seronegative Healthcare Workers

by Byungki Jang, Han Wool Kim, Han-Sung Kim, Ji Young Park, Hyeonji Seo and Yong Kyun Kim

Vaccines 2022, 10(11), 1812; https://doi.org/10.3390/vaccines10111812 - 28 Oct 2022

Cited by 2 | Viewed by 2508

Abstract

Although there have been several studies regarding the immunogenicity of one or two booster doses of the measles–mumps–rubella (MMR) vaccine in measles-seronegative young adults, limited data are available about how long the immune response is sustained compared with natural infection. This study included [...] Read more.

Although there have been several studies regarding the immunogenicity of one or two booster doses of the measles–mumps–rubella (MMR) vaccine in measles-seronegative young adults, limited data are available about how long the immune response is sustained compared with natural infection. This study included seronegative healthcare workers (HCWs) (aged 21–38 years) who received one or two doses of the measles–mumps–rubella (MMR) vaccine and HCWs with laboratory-confirmed measles infection during an outbreak in 2019. We compared neutralizing antibody titers measured using the plaque reduction neutralization (PRN) test and measles-specific immunoglobulin G (IgG) using chemiluminescent immunoassays 2 years after vaccination or infection. Among 107 HCWs with seronegative measles IgGs, the overall seroconversion rate of measles IgGs remained 82.2% (88/107), and 45.8% (49/107) of the participants had a medium (121–900) or high (>900) PRN titer after 2 years from one or two booster doses. The measles-neutralizing antibody titers of both PRN titer (ND50) and geometric mean concentration 2 years after natural infection were significantly higher than those of one or two booster doses of the MMR vaccine (p < 0.001 and p < 0.001, respectively). Our results suggest that serologic screening followed by appropriate postexposure prophylaxis can be beneficial for young HCWs without a history of natural infection especially in a measles outbreak setting, because of possible susceptibility to measles despite booster MMR vaccination 2 years ago. Long-term data about sustainable humoral immunity after one or two booster vaccination are needed based on the exact vaccination history. Full article

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15 pages, 2854 KiB

Open AccessArticle

Immunoinformatics Studies and Design of a Potential Multi-Epitope Peptide Vaccine to Combat the Fatal Visceral Leishmaniasis

by Olugbenga Samson Onile, Fungai Musaigwa, Nimibofa Ayawei, Victor Omoboyede, Tolulope Adelonpe Onile, Eyarefe Oghenevovwero and Raphael Taiwo Aruleba

Vaccines 2022, 10(10), 1598; https://doi.org/10.3390/vaccines10101598 - 22 Sep 2022

Cited by 6 | Viewed by 2267

Abstract

Leishmaniasis is a neglected tropical disease caused by parasitic intracellular protozoa of the genus Leishmania. The visceral form of this disease caused by Leishmania donovani continues to constitute a major public health crisis, especially in countries of endemicity. In some cases, it [...] Read more.

Leishmaniasis is a neglected tropical disease caused by parasitic intracellular protozoa of the genus Leishmania. The visceral form of this disease caused by Leishmania donovani continues to constitute a major public health crisis, especially in countries of endemicity. In some cases, it is asymptomatic and comes with acute and chronic clinical outcomes such as weight loss, pancytopenia, hepatosplenomegaly, and death if left untreated. Over the years, the treatment of VL has relied solely on chemotherapeutic agents, but unfortunately, these drugs are now faced with challenges. Despite all efforts, no successful vaccine has been approved for VL. This could be as a result of limited knowledge/understanding of the immune mechanisms necessary to regulate parasite growth. Using a computational approach, this study explored the prospect of harnessing the properties of a disulfide isomerase protein of L. donovani amastigotses to develop a multi-epitope subunit vaccine candidate against the parasite. We designed a 248-amino acid multi-epitope vaccine with a predicted antigenicity probability of 0.897372. Analyses of immunogenicity, allergenicity, and multiple physiochemical parameters indicated that the constructed vaccine candidate was stable, non-allergenic, and immunogenic, making it compatible with humans and hence, a potentially viable and safe vaccine candidate against Leishmania spp. Parasites. Full article

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13 pages, 2020 KiB

Open AccessArticle

Multi-Epitope-Based Vaccine Candidate for Monkeypox: An In Silico Approach

by Sayed Aliul Hasan Abdi, Amena Ali, Shabihul Fatma Sayed, Abutahir, Abuzer Ali and Prawez Alam

Vaccines 2022, 10(9), 1564; https://doi.org/10.3390/vaccines10091564 - 19 Sep 2022

Cited by 32 | Viewed by 4314

Abstract

Currently, there are limited treatment options available for the monkeypox disease. We used a computational strategy to design a specific antigenic vaccine against pathogens. After using various immunoinformatic tools and filters, cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon gamma (IFN-γ)-inducing [...] Read more.

Currently, there are limited treatment options available for the monkeypox disease. We used a computational strategy to design a specific antigenic vaccine against pathogens. After using various immunoinformatic tools and filters, cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon gamma (IFN-γ)-inducing epitopes, which comprised the vaccine, in addition to other parameters, such as antigenic and allergic profiles, were assessed to confirm the safety of the vaccine. However, vaccine interaction and stability with Toll-like receptors (TLRs) were assessed by dynamic simulation methods, and it was found that the constructed vaccine was stable. In addition, C-IMMSIM tools were used to determine the immune-response-triggering capabilities of the vaccine. These immunoinformatic findings reveal that constructed vaccine candidates may be capable of triggering an efficient immune response for monkeypox viral infections. However, experimental evaluation is required to verify the safety and immunogenic profile of constructed vaccines. Full article

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22 pages, 986 KiB

Open AccessSystematic Review

The Impact of COVID-19 Pandemic on Inequity in Routine Childhood Vaccination Coverage: A Systematic Review

by Nicholas Spencer, Wolfgang Markham, Samantha Johnson, Emmanuelle Arpin, Rita Nathawad, Geir Gunnlaugsson, Nusrat Homaira, Maria Lucia Mesa Rubio and Catalina Jaime Trujillo

Vaccines 2022, 10(7), 1013; https://doi.org/10.3390/vaccines10071013 - 24 Jun 2022

Cited by 22 | Viewed by 3738

Abstract

Background: Routine childhood vaccination coverage rates fell in many countries during the COVID-19 pandemic, but the impact of inequity on coverage is unknown. Methods: We synthesised evidence on inequities in routine childhood vaccination coverage (PROSPERO, CRD 42021257431). Studies reporting empirical data on routine [...] Read more.

Background: Routine childhood vaccination coverage rates fell in many countries during the COVID-19 pandemic, but the impact of inequity on coverage is unknown. Methods: We synthesised evidence on inequities in routine childhood vaccination coverage (PROSPERO, CRD 42021257431). Studies reporting empirical data on routine vaccination coverage in children 0–18 years old during the COVID-19 pandemic by equity stratifiers were systematically reviewed. Nine electronic databases were searched between 1 January 2020 and 18 January 2022. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Tool for Cohort Studies. Overall, 91 of 1453 studies were selected for full paper review, and thirteen met the inclusion criteria. Results: The narrative synthesis found moderate evidence for inequity in reducing the vaccination coverage of children during COVID-19 lockdowns and moderately strong evidence for an increase in inequity compared with pre-pandemic months (before March 2020). Two studies reported higher rates of inequity among children aged less than one year, and one showed higher inequity rates in middle- compared with high-income countries. Conclusions: Evidence from a limited number of studies shows the effect of the pandemic on vaccine coverage inequity. Research from more countries is required to assess the global effect on inequity in coverage. Full article

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24 pages, 2051 KiB

Open AccessReview

Systematic Review on Pathophysiological Complications in Severe COVID-19 among the Non-Vaccinated and Vaccinated Population

by Ali A. Rabaan, Muhammed A. Bakhrebah, Abbas Al Mutair, Saad Alhumaid, Jumana M. Al-Jishi, Jehad AlSihati, Hawra Albayat, Ahmed Alsheheri, Mohammed Aljeldah, Mohammed Garout, Wadha A. Alfouzan, Yousef N. Alhashem, Salma AlBahrani, Saleh A. Alshamrani, Sultan Alotaibi, Abdullah A. AlRamadhan, Hanadi N. Albasha, Khalid Hajissa and Mohamad-Hani Temsah

Vaccines 2022, 10(7), 985; https://doi.org/10.3390/vaccines10070985 - 21 Jun 2022

Cited by 12 | Viewed by 3916

Abstract

COVID-19, caused by SARS-CoV-2, is one of the longest viral pandemics in the history of mankind, which have caused millions of deaths globally and induced severe deformities in the survivals. For instance, fibrosis and cavities in the infected lungs of COVID-19 are some [...] Read more.

COVID-19, caused by SARS-CoV-2, is one of the longest viral pandemics in the history of mankind, which have caused millions of deaths globally and induced severe deformities in the survivals. For instance, fibrosis and cavities in the infected lungs of COVID-19 are some of the complications observed in infected patients post COVID-19 recovery. These health abnormalities, including is multiple organ failure—the most striking pathological features of COVID-19—have been linked with diverse distribution of ACE2 receptor. Additionally, several health complications reports were reported after administration of COVID-19 vaccines in healthy individuals, but clinical or molecular pathways causing such complications are not yet studied in detail. Thus, the present systematic review established the comparison of health complication noted in vaccinated and non-vaccinated individuals (COVID-19 infected patients) to identify the association between vaccination and the multiorgan failure based on the data obtained from case studies, research articles, clinical trials/Cohort based studies and review articles published between 2020–2022. This review also includes the biological rationale behind the COVID-19 infection and its subsequent symptoms and effects including multiorgan failure. In addition, multisystem inflammatory syndrome (MIS) has been informed in individuals post vaccination that resulted in multiorgan failure but, no direct correlation of vaccination with MIS has been established. Similarly, hemophagocytic lymphohistiocytosis (HLH) also noted to cause multiorgan failure in some individuals following full vaccination. Furthermore, severe complications were recorded in elderly patients (+40 years of age), indicates that older age individuals are higher risk by COVID-19 and post vaccination, but available literature is not sufficient to comply with any conclusive statements on relationship between vaccination and multiorgan failure. Full article

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18 pages, 2960 KiB

Open AccessArticle

Public Health Value of a Hypothetical Pneumococcal Conjugate Vaccine (PCV) Introduction: A Case Study

by Nathorn Chaiyakunapruk, Dayoung Song, Julia Lynch, Jerome H. Kim, Piyameth Dilokthornsakul, Tawee Chotpitayasunondh and Vittal Mogasale

Vaccines 2022, 10(6), 950; https://doi.org/10.3390/vaccines10060950 - 15 Jun 2022

Viewed by 2581

Abstract

Background: Understanding the public health value of a vaccine at an early stage of development helps in valuing and prioritizing the investment needed. Here we present the potential cost-effectiveness of an upcoming 12 valent pneumococcal conjugate vaccine (PCV 12) in the case study [...] Read more.

Background: Understanding the public health value of a vaccine at an early stage of development helps in valuing and prioritizing the investment needed. Here we present the potential cost-effectiveness of an upcoming 12 valent pneumococcal conjugate vaccine (PCV 12) in the case study country, Thailand. Methods: The cost-effectiveness analysis included a hypothetical scenario of three doses (2 + 1 regimen) PCV12 introduction in the national immunization program of Thailand compared to no PCV, PCV10, and PCV13 among <6 months old from a societal perspective with a lifetime horizon and one-year cycle length. Data from Thailand, as well as assumptions supported by the literature, were used in the analysis. The price of PCV12 was assumed similar to that of PCV10 or PCV13 for GAVI’s eligible countries based on inputs from stakeholder meeting. A one-way sensitivity analysis was conducted using 0.5–1.5 times the base price of PCV12. Results were presented in incremental cost-effectiveness ratio (ICER) in terms of monetary value per quality-adjusted life-year (QALY) gained. Results: Vaccination with PCV12 among a hypothetical cohort of 100,000 Thai children is expected to avert a total of 5358 cases which includes 5 pneumococcal meningitis, 43 pneumococcal bacteremia, 5144 all-cause pneumonia, and 166 all-cause acute otitis media compared to no vaccination. The national PCV12 vaccination program is a cost-saving strategy compared to the other three strategies. The one-way sensitivity analysis showed PCV12 is a cost-saving strategy when 1.5 times the base price of PCV12 was assumed. Conclusions: Within the limitations of hypothetical assumptions and price points incorporated, the study indicates the potential public health value of PCV12 in Thailand. Full article

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22 pages, 3241 KiB

Open AccessArticle

Evaluation of HSV-2 gE Binding to IgG-Fc and Application for Vaccine Development

by Jennifer D. Galli, Melanie Horton, Eberhard Durr, Gwendolyn J. Heidecker, Daniel Freed, Arthur Fridman, Dai Wang and Lan Zhang

Vaccines 2022, 10(2), 184; https://doi.org/10.3390/vaccines10020184 - 25 Jan 2022

Cited by 2 | Viewed by 3289

Abstract

Glycoprotein E (gE) and glycoprotein I (gI) are expressed as a heterodimer on the surface of Herpes simplex virus (HSV). Glycoprotein E binds Fc domain of immunoglobulin G (IgG) and inhibits activities mediated by the IgG Fc domain, contributing to immune evasion by [...] Read more.

Glycoprotein E (gE) and glycoprotein I (gI) are expressed as a heterodimer on the surface of Herpes simplex virus (HSV). Glycoprotein E binds Fc domain of immunoglobulin G (IgG) and inhibits activities mediated by the IgG Fc domain, contributing to immune evasion by HSV. It has been reported that HSV type 1 gE (gE-1) is capable of binding IgG Fc as a monomer and in a heterodimeric complex with gI, with the heterodimer having 50- to100-fold greater affinity for Fc than gE alone. We report the production of both a soluble form of HSV type 2 gE (gE-2) and a soluble HSV-2 gE/gI heterodimer (gE-2/gI-2). Characterization of soluble gE-2 by surface plasmon resonance (SPR) demonstrates that it is incapable of binding human IgG or the IgG Fc domain. Co-expression with HSV-2 gI (gI-2) and purification of the gE-2/gI-2 heterodimer enable gE-2 to bind human IgG through its Fc domain. We hypothesize that functional epitopes of wildtype gE-2 may be masked by plasma IgG Fc and affect the immunogenicity of the gE-2/gI-2 heterodimer as a vaccine antigen. A series of gE-2 mutations within the surface-exposed Fc:gE-2 interface was designed, and gE-2 mutants were co-expressed with gI-2. Evaluation of twelve gE-2 mutant heterodimers by SPR assay identified nine gE-2 mutations which abrogated or reduced Fc binding while maintaining heterodimer formation with gI. Vaccinating rabbits with the four most Fc-binding deficient gE-2/gI-2 heterodimers elicited comparable anti-heterodimer binding antibody titers and statistically significantly higher serum neutralization antibody levels than wildtype heterodimers. Taken together, these data support the concept of rational antigen design for improved vaccine candidates. Full article

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13 pages, 2907 KiB

Open AccessArticle

Predictors of Survival after Vaccination in a Pneumonic Plague Model

by Barry D. Moore, Clair Macleod, Lisa Henning, Robert Krile, Ying-Liang Chou, Thomas R. Laws, Wendy A. Butcher, Kristoffer M. Moore, Nicola J. Walker, Ethel Diane Williamson and Darrell R. Galloway

Vaccines 2022, 10(2), 145; https://doi.org/10.3390/vaccines10020145 - 19 Jan 2022

Cited by 7 | Viewed by 2095

Abstract

Background: The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Methods: Here we have used a murine model of pneumonic plague to examine [...] Read more.

Background: The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Methods: Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination. We varied vaccine type, as either a genetic fusion of the F1 and V protein antigens or a mixture of these two recombinant antigens, as well as antigen dose-level and formulation in order to correlate immune response to survival. Results: Whilst there was interaction between each of the variables of vaccine type, dose level and formulation and these all contributed to survival, vaccine formulation in protein-coated microcrystals (PCMCs) was the key contributor in inducing antibody titres. From these data, we propose a cut-off in total serum antibody titre to the F1 and V proteins of 100 µg/mL and 200 µg/mL, respectively. At these thresholds, survival is predicted in this murine pneumonic model to be >90%. Within the total titre of antibody to the V antigen, the neutralising antibody component correlated with dose level and was enhanced when the V antigen in free form was formulated in PCMCs. Antibody titre to F1 was limited by fusion to V, but this was compensated for by PCMC formulation. Conclusions: These data will enable clinical assessment of this and other candidate plague vaccines that utilise the same vaccine antigens by identifying a target antibody titre from murine models, which will guide the evaluation of clinical titres as serological surrogate markers of efficacy. Full article

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26 pages, 3654 KiB

Open AccessArticle

Age and Primary Vaccination Background Influence the Plasma Cell Response to Pertussis Booster Vaccination

by Annieck M. Diks, Pauline Versteegen, Cristina Teodosio, Rick J. Groenland, Bas de Mooij, Anne-Marie Buisman, Alba Torres-Valle, Martín Pérez-Andrés, Alberto Orfao, Guy A. M. Berbers, Jacques J. M. van Dongen, Magdalena A. Berkowska and on behalf of the IMI-2 PERISCOPE Consortium

Vaccines 2022, 10(2), 136; https://doi.org/10.3390/vaccines10020136 - 18 Jan 2022

Cited by 12 | Viewed by 3102

Abstract

Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole-cell to acellular pertussis vaccines, although other factors may also contribute. Here, [...] Read more.

Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole-cell to acellular pertussis vaccines, although other factors may also contribute. Here, we applied high-dimensional flow cytometry to investigate changes in B cells in individuals of different ages and distinct priming backgrounds upon administration of an acellular pertussis booster vaccine. Participants were divided over four age cohorts. We compared longitudinal kinetics within each cohort and between the different cohorts. Changes in the B-cell compartment were correlated to numbers of vaccine-specific B- and plasma cells and serum Ig levels. Expansion and maturation of plasma cells 7 days postvaccination was the most prominent cellular change in all age groups and was most pronounced for more mature IgG1+ plasma cells. Plasma cell responses were stronger in individuals primed with whole-cell vaccine than in individuals primed with acellular vaccine. Moreover, IgG1+ and IgA1+ plasma cell expansion correlated with FHA-, Prn-, or PT- specific serum IgG or IgA levels. Our study indicates plasma cells as a potential early cellular marker of an immune response and contributes to understanding differences in immune responses between age groups and primary vaccination backgrounds. Full article

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11 pages, 2130 KiB

Open AccessArticle

Antibody Levels at 3-Years Follow-Up of a Third Dose of Measles-Mumps-Rubella Vaccine in Young Adults

by Patricia Kaaijk, Alienke J. Wijmenga-Monsuur, Hinke I. ten Hulscher, Jeroen Kerkhof, Gaby Smits, Mioara Alina Nicolaie, Marianne A. van Houten and Rob S. van Binnendijk

Vaccines 2022, 10(1), 132; https://doi.org/10.3390/vaccines10010132 - 17 Jan 2022

Cited by 10 | Viewed by 3086

Abstract

Mumps outbreaks and breakthrough infections of measles and rubella have raised concerns about waning of vaccine-induced immunity after two doses of measles-mumps-rubella (MMR) vaccination. In the present follow-up study, serum IgG antibodies against mumps, measles and rubella, as well as the functional neutralizing [...] Read more.

Mumps outbreaks and breakthrough infections of measles and rubella have raised concerns about waning of vaccine-induced immunity after two doses of measles-mumps-rubella (MMR) vaccination. In the present follow-up study, serum IgG antibodies against mumps, measles and rubella, as well as the functional neutralizing antibodies against both the mumps vaccine strain and mumps outbreak strains were measured longitudinally in young adults that received a third MMR (MMR3) dose. The mumps-specific IgG and virus neutralizing antibody levels at 3 years after vaccination were still elevated compared to pre-vaccination antibody levels, although the differences were smaller than at earlier timepoints. Interestingly, subjects with low antibody levels to mumps before vaccination benefited the most as they showed the strongest antibody increase after an MMR3 dose. Three years after an MMR3 dose, all subjects had antibody levels to measles and rubella above the internationally agreed antibody cutoff levels for clinical protection. Our data support the recommendation that an MMR3 dose may provide additional protection for those that have become susceptible to mumps virus infection during outbreaks. MMR3 also resulted in an increase in anti-measles and rubella antibody levels that lasted longer than might have been expected. Full article

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12 pages, 1250 KiB

Open AccessArticle

Development and Properties of Francisella tularensis Subsp. holarctica 15 NIIEG Vaccine Strain without the recD Gene

by Vitaly Pavlov, Galina Vakhrameeva, Alexander Mokrievich, Mikhail E. Platonov, Galina Titareva, Raisa Mironova, Tatiana Kombarova, Tatiana Gapelchenkova and Ivan Dyatlov

Vaccines 2022, 10(1), 108; https://doi.org/10.3390/vaccines10010108 - 11 Jan 2022

Cited by 1 | Viewed by 1963

Abstract

The genomic analysis of all subspecies F. tularensis, as found in Gen Bank NCBI, reveals the presence of genes encoding proteins like to the multifunctional RecBCD enzyme complex in E. coli and other bacteria. To date, the role of the recD gene [...] Read more.

The genomic analysis of all subspecies F. tularensis, as found in Gen Bank NCBI, reveals the presence of genes encoding proteins like to the multifunctional RecBCD enzyme complex in E. coli and other bacteria. To date, the role of the recD gene in F. tularensis, which encodes the alpha chain of exonuclease V, in DNA metabolism processes, has not been studied either in vitro or in vivo. F. tularensis subsp. holarctica 15 NIIEG, a vaccine strain, served as the basis to create the F. tularensis 15D strain with recD deletion. The lack of the recD gene suppresses the integration of suicide plasmids with F. tularensis genome fragments into the chromosome. The modified strain showed reduced growth in vitro and in vivo. This study shows that such deletion significantly reduces the virulence of the strain in BALB/c mice. Full article

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13 pages, 2010 KiB

Open AccessArticle

Immunity to Sda1 Protects against Infection by Sda1⁺ and Sda1⁻ Serotypes of Group A Streptococcus

by Shuai Bi, Jie Wang, Meiyi Xu, Ning Li and Beinan Wang

Vaccines 2022, 10(1), 102; https://doi.org/10.3390/vaccines10010102 - 11 Jan 2022

Cited by 1 | Viewed by 1858

Abstract

Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not [...] Read more.

Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not been determined. In this study, we explored the potential of Sda1 as a vaccine candidate. Sda1 was used as a vaccine to immunize mice intranasally. The effect of anti-Sda1 IgG in neutralizing degradation of NETs was determined and the protective role of Sda1 was investigated with intranasal and systemic challenge models. Antigen-specific antibodies were induced in the sera and pharyngeal mucosal site after Sda1 immunization. The anti-Sda1 IgG efficiently prevented degradation of NETs by supernatant samples from different GAS serotypes with or without Sda1. Sda1 immunization promoted clearance of GAS from the nasopharynx independent of GAS serotypes but did not reduce lethality after systemic GAS challenge. Anti-Sda1 antibody can neutralize degradation of NETs by Sda1 and other phage-encoded DNases and decrease GAS colonization at the nasopharynx across serotypes. These results indicate that Sda1 can be a potential vaccine candidate for reduction in GAS reservoir and GAS tonsillitis-associated diseases. Full article

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15 pages, 2280 KiB

Open AccessArticle

Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines

by Christina Sølund, Alexander P. Underwood, Carlota Fernandez-Antunez, Signe Bollerup, Lotte S. Mikkelsen, Signe Lysemose Villadsen, Ulrik Fahnøe, Anni Assing Winckelmann, Shan Feng, Caroline A. Nørløv Vinten, Magnus Illum Dalegaard, Greta Vizgirda, Anna-Louise Sørensen, Santseharay Ramirez, Jens Bukh and Nina Weis

Vaccines 2022, 10(1), 75; https://doi.org/10.3390/vaccines10010075 - 4 Jan 2022

Cited by 11 | Viewed by 2890

Abstract

With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated [...] Read more.

With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty^®, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria^®, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty^® or Spikevax^®, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID₅₀: 2525, IQR: 1667–4313) and vector–mRNA (ID₅₀: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID₅₀: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria^® (p = 0.0072). Between mRNA–mRNA and vector–mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure. Full article

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2021

Jump to: 2024, 2023, 2022

14 pages, 1322 KiB

Open AccessArticle

Has Clinical and Epidemiological Varicella Burden Changed over Time in Children? Overview on Hospitalizations, Comorbidities and Costs from 2010 to 2017 in Italy

by Maria Francesca Piazza, Daniela Amicizia, Chiara Paganino, Francesca Marchini, Matteo Astengo, Federico Grammatico, Cecilia Trucchi, Paolo Romairone, Simona Simonetti, Camilla Sticchi and Filippo Ansaldi

Vaccines 2021, 9(12), 1485; https://doi.org/10.3390/vaccines9121485 - 15 Dec 2021

Cited by 4 | Viewed by 3031

Abstract

According to WHO estimates, varicella disease is responsible of a worldwide significant burden in terms of hospitalizations, complications, and deaths, with more than 90% of cases under 12 years old. This study aims at evaluating the clinical, epidemiological, and economic burden of varicella [...] Read more.

According to WHO estimates, varicella disease is responsible of a worldwide significant burden in terms of hospitalizations, complications, and deaths, with more than 90% of cases under 12 years old. This study aims at evaluating the clinical, epidemiological, and economic burden of varicella in Ligurian children, about comorbidities, organizational variables, and vaccination coverages from 2010 to 2017, in terms of Emergency Department accesses and hospitalizations. The overall hospitalization rate was 179.76 (per 100,000 inhab.), with a gradual but significant decline since 2015, when universal varicella vaccination was introduced in Liguria (p < 0.0001). The risk of being hospitalized for complicated varicella in subjects with at least one comorbidity was significantly higher than in subjects without comorbidities (p = 0.0016). The economic analysis showed higher costs in subjects with complicated varicella who were 0–3 years old. This age group showed higher costs also considering extra-hospital costs for both outpatient procedures and pharmaceutical costs (p < 0.0001). The results confirm the relevant burden of varicella, especially in the 0–3 age group and in children with comorbidities. Thus, vaccination with the achievement of adequate vaccination coverages is confirmed to be a necessary control strategy to reduce hospitalizations and associated complications with important economic benefits. Full article

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11 pages, 970 KiB

Open AccessFeature PaperArticle

12 Months Persistent Immunogenicity after Hepatitis B Vaccination in Patients with Type 2 Diabetes and Immunogenicity of Revaccination in Non-Responders: An Open-Label Randomized Controlled Trial

by Bingfeng Han, Wu Liu, Juan Du, Hanyu Liu, Tianshuo Zhao, Shubo Yang, Shuai Wang, Sihui Zhang, Bei Liu, Yaqiong Liu and Fuqiang Cui

Vaccines 2021, 9(12), 1407; https://doi.org/10.3390/vaccines9121407 - 29 Nov 2021

Cited by 1 | Viewed by 2320

Abstract

Background: In initial studies, the immunogenicity and safety of hepatitis B vaccines in patients with diabetes has been assessed in China. Methods: In six township health centers in Gansu Province, 232 diabetic patients and 77 healthy people were allocated to receive two 3-dose [...] Read more.

Background: In initial studies, the immunogenicity and safety of hepatitis B vaccines in patients with diabetes has been assessed in China. Methods: In six township health centers in Gansu Province, 232 diabetic patients and 77 healthy people were allocated to receive two 3-dose hepatitis B vaccines (Group D20SC 0-1-6; Group D20CHO 0-1-6; Group ND20SC 0-1-6). Participants were followed up at 12 months after being fully vaccinated. One dose of the vaccine was randomly administered to non-responders. Chi-square test was used to compare the differences in response rate between two groups. Results: The anti-HBs response rates of three groups decreased from 84.1%, 89.1% and 88.3% at one month to 64.6%, 79.8% and 71.4% at twelve months. There was no statistical difference in the immune response rates between Group D20SC 0-1-6 and Group ND20SC 0-1-6; however, that of Group D20CHO 0-1-6 was higher than that of Group D20SC 0-1-6. After revaccination, the geometric mean concentrations were 491.7 mIU/mL and 29.7 mIU/mL after using vaccines containing 60 μg and 20 μg HBsAg. Conclusions: At 12 months, immune response in diabetic patients were not significantly different from that in healthy people. Revaccination with one dose of hepatitis B vaccine containing 60 μg HBsAg for non-responders was more satisfactory. Full article

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11 pages, 1729 KiB

Open AccessArticle

Side Effects of COVID-19 Pfizer-BioNTech mRNA Vaccine in Children Aged 12–18 Years in Saudi Arabia

by Edrous Alamer, Abdulaziz Alhazmi, Naaif A. Qasir, Rahaf Alamer, Halima Areeshi, Gassem Gohal, Marwa Qadri, Anwar M. Hashem and Abdullah Algaissi

Vaccines 2021, 9(11), 1297; https://doi.org/10.3390/vaccines9111297 - 9 Nov 2021

Cited by 35 | Viewed by 11274

Abstract

Background: Massive vaccination campaigns have been undertaken globally to combat the spread of the Coronavirus Disease 2019 (COVID-19). While most COVID-19 vaccines have shown excellent efficacy and safety profiles in clinical studies, real-world monitoring of vaccine safety is still important. In this [...] Read more.

Background: Massive vaccination campaigns have been undertaken globally to combat the spread of the Coronavirus Disease 2019 (COVID-19). While most COVID-19 vaccines have shown excellent efficacy and safety profiles in clinical studies, real-world monitoring of vaccine safety is still important. In this study, we aimed to investigate the early side effects of Pfizer-BioNTech (BNT162b2) mRNA vaccine in children between 12–18 years old in Saudi Arabia. Method: To investigate the side effects in children in this age range following the administration of either one or two doses of Pfizer-BioNTech (BNT162b2) mRNA vaccine, we conducted a retrospective, cross-sectional study using a self-administered online survey. General and demographic data were collected, and vaccine-associated side effects following vaccination were evaluated. Results: The study recruited a total of 965 eligible participants. Overall, 571 (60%) of the study participants reported at least one side effect following Pfizer-BioNTech (BNT162b2) mRNA vaccination. The most frequently reported side effects were pain or redness at the site of injection (90%), fatigue (67%), fever (59%), headache (55%), nausea or vomiting (21%), and chest pain and shortness of breath (20%). Joint or bone pain were reported less frequently among our participants (2%). Our data showed that more female participants reported side effects compared to male participants, with 52% and 48%, respectively. Side effects were more common after the second dose compared to the first dose in our study cohort. Conclusions: While 60% of the children (12–18 years old) who received Pfizer-BioNTech (BNT162b2) mRNA vaccine reported side effects, our data showed that these side effects were not different from those that were reported in the clinical trials which lasted only for a few days. Side effects were more common after the second dose. Larger epidemiological and molecular studies are needed to evaluate the safety and the effectiveness of COVID-19 vaccine in protection of children against SARS-CoV-2 reinfections. Full article

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17 pages, 4736 KiB

Open AccessArticle

Avian Cell Line DuckCelt^®-T17 Is an Efficient Production System for Live-Attenuated Human Metapneumovirus Vaccine Candidate Metavac^®

by Caroline Chupin, Andrés Pizzorno, Aurélien Traversier, Pauline Brun, Daniela Ogonczyk-Makowska, Blandine Padey, Cédrine Milesi, Victoria Dulière, Emilie Laurent, Thomas Julien, Marie Galloux, Bruno Lina, Jean-François Eléouët, Karen Moreau, Marie-Eve Hamelin, Olivier Terrier, Guy Boivin, Julia Dubois and Manuel Rosa-Calatrava

Vaccines 2021, 9(10), 1190; https://doi.org/10.3390/vaccines9101190 - 16 Oct 2021

Cited by 5 | Viewed by 3076

Abstract

The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with [...] Read more.

The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with traditional cell platforms used for viral vaccine manufacture. We investigated whether the DuckCelt^®-T17 avian cell line (Vaxxel), previously described as an efficient production system for several influenza strains, could also be used to produce a new HMPV LAV candidate (Metavac^®, SH gene-deleted A1/C-85473 HMPV). To that end, we characterized the operational parameters of MOI, cell density, and trypsin addition to achieve the optimal production of Metavac^®, and demonstrated that the DuckCelt^®-T17 cell line is permissive and well-adapted to the production of the wild-type A1/C-85473 HMPV and the Metavac^® vaccine candidate. Moreover, our results confirmed that the LAV candidate produced in DuckCelt^®-T17 cells conserves its advantageous replication properties in LLC-MK2 and 3D-reconstituted human airway epithelium models, and its capacity to induce efficient neutralizing antibodies in a BALB/c mouse model. Our results suggest that the DuckCelt^®-T17 avian cell line is a very promising platform for the scalable in-suspension serum-free production of the HMPV-based LAV candidate Metavac^®. Full article

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23 pages, 423 KiB

Open AccessReview

COVID-19 Vaccinations: A Comprehensive Review of Their Safety and Efficacy in Special Populations

by Zhipeng Yan, Ming Yang and Ching-Lung Lai

Vaccines 2021, 9(10), 1097; https://doi.org/10.3390/vaccines9101097 - 28 Sep 2021

Cited by 30 | Viewed by 6152

Abstract

COVID-19 has been spreading worldwide since late 2019. There is no definitive cure to date. Global vaccination programs are urgently required to confer herd immunity, reducing the incidence of COVID-19 infections and associated morbidity and mortality. However, a significant proportion of special populations [...] Read more.

COVID-19 has been spreading worldwide since late 2019. There is no definitive cure to date. Global vaccination programs are urgently required to confer herd immunity, reducing the incidence of COVID-19 infections and associated morbidity and mortality. However, a significant proportion of special populations are hesitant to receive vaccination due to their special conditions, namely, age (pediatrics and geriatrics), immunocompromised state, autoimmune diseases, chronic cardiovascular and pulmonary conditions, active or treated cancers, and pregnancy. This review aims to evaluate the existing evidence of COVID-19 vaccinations on these special populations and to provide clues to guide vaccination decision making to balance the benefits and risks of vaccinations. Full article

11 pages, 233 KiB

Open AccessFeature PaperArticle

Hepatitis B Vaccination Coverage Rates and Associated Factors: A Community-Based, Cross-Sectional Study Conducted in Beijing, 2019–2020

by Yan Liang, Xinxin Bai, Xinyao Liu, Zheng Zhang, Xinghuo Pang, Li Nie, Wuqi Qiu, Wei Zhao and Guangyu Hu

Vaccines 2021, 9(10), 1070; https://doi.org/10.3390/vaccines9101070 - 24 Sep 2021

Cited by 6 | Viewed by 2548

Abstract

Hepatitis B vaccination coverage rates are low throughout most populations in China. Factors influencing low coverage rates, including population-specific hepatitis B vaccination barriers, may inform policies that promote vaccination. A cross-sectional survey of residents from 43 communities assessed their vaccination status and identified [...] Read more.

Hepatitis B vaccination coverage rates are low throughout most populations in China. Factors influencing low coverage rates, including population-specific hepatitis B vaccination barriers, may inform policies that promote vaccination. A cross-sectional survey of residents from 43 communities assessed their vaccination status and identified associated factors via uni- and multivariable logistic regression and subgroup analyses. In total, 11,280 of 36,007 respondents received a hepatitis B vaccine, indicating a 31.33% coverage rate. Multivariable logistic regression revealed non-Beijing (odds ratio (OR) = 0.81; 95% confidence interval (CI): 0.76–0.85) and residents who self-rated their health as very healthy (OR = 0.82; 95% CI: 0.68–0.99) were unlikely to be vaccinated. Farmers (OR = 1.68; 95% CI: 1.51–1.86), commerce and service workers (OR = 1.82; 95% CI, 1.63–2.04), government employees (OR = 1.56; 95% CI: 1.38–1.77), professionals and technicians (OR = 1.85; 95% CI: 1.63–2.09), and students (OR = 1.69; 95% CI: 1.10–2.59) had increased hepatitis B vaccination rates. The multivariable assessment revealed hepatitis B vaccination coverage rates are associated with confirmed or suspected family cases, vaccination unwillingness or uncertainty, and unawareness of its prevention of the hepatitis B virus. Low hepatitis B vaccination coverage rates among Beijing subpopulations highlight the need for improved strategies, including those that target specific populations. Full article

17 pages, 571 KiB

Open AccessReview

An Update on mRNA-Based Viral Vaccines

by Subbiah Jeeva, Ki-Hye Kim, Chong Hyun Shin, Bao-Zhong Wang and Sang-Moo Kang

Vaccines 2021, 9(9), 965; https://doi.org/10.3390/vaccines9090965 - 29 Aug 2021

Cited by 16 | Viewed by 8696

Abstract

With the success of COVID-19 vaccines, newly created mRNA vaccines against other infectious diseases are beginning to emerge. Here, we review the structural elements required for designing mRNA vaccine constructs for effective in vitro synthetic transcription reactions. The unprecedently speedy development of mRNA [...] Read more.

With the success of COVID-19 vaccines, newly created mRNA vaccines against other infectious diseases are beginning to emerge. Here, we review the structural elements required for designing mRNA vaccine constructs for effective in vitro synthetic transcription reactions. The unprecedently speedy development of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was enabled with previous innovations in nucleoside modifications during in vitro transcription and lipid nanoparticle delivery materials of mRNA. Recent updates are briefly described in the status of mRNA vaccines against SARS-CoV-2, influenza virus, and other viral pathogens. Unique features of mRNA vaccine platforms and future perspectives are discussed. Full article

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10 pages, 2556 KiB

Open AccessArticle

In Vitro Priming of Human T Cells by Dendritic Cells Provides a Screening Tool for Candidate Vaccines for Burkholderia pseudomallei

by Durga Reddi, Lydia Durant, David Bernardo, Alistair Noble, Nicholas R. English, Philip Hendy, Graeme C. Clark, Joann L. Prior, Ethel Diane Williamson and Stella C. Knight

Vaccines 2021, 9(8), 929; https://doi.org/10.3390/vaccines9080929 - 22 Aug 2021

Cited by 5 | Viewed by 3831

Abstract

Murine dendritic cells, when pulsed with heat-killed Burkholderia pseudomallei and used to immunise naïve mice, have previously been shown to induce protective immunity in vivo. We have now demonstrated the in vitro priming of naïve human T cells against heat-killed B. pseudomallei [...] Read more.

Murine dendritic cells, when pulsed with heat-killed Burkholderia pseudomallei and used to immunise naïve mice, have previously been shown to induce protective immunity in vivo. We have now demonstrated the in vitro priming of naïve human T cells against heat-killed B. pseudomallei, by co-culture with syngeneic B. pseudomallei-pulsed dendritic cells. Additionally, we have enriched the DC fraction such that a study of the differential response induced by pulsed DCs of either myeloid or plasmacytoid lineage in syngeneic human T cells was achievable. Whilst both mDCs and pDCs were activated by pulsing, the mDCs contributed the major response to B. pseudomallei with the expression of the migration marker CCR7 and a significantly greater secretion of the proinflammatory TNFα and IL1β. When these DC factions were combined and used to prime syngeneic T cells, a significant proliferation was observed in the CD4⁺ fraction. Here, we have achieved human T cell priming in vitro with unadjuvanted B. pseudomallei, the causative organism of melioidosis, for which there is currently no approved vaccine. We propose that the approach we have taken could be used to screen for the human cellular response to candidate vaccines and formulations, in order to enhance the cell-mediated immunity required to protect against this intracellular pathogen and potentially more broadly against other, difficult-to-treat intracellular pathogens. To date, the polysaccharide capsule of B. pseudomallei, fused to a standard carrier protein, e.g., Crm, looks a likely vaccine candidate. Dendritic cells (DCs), providing, as they do, the first line of defence to infection, process and present microbial products to the immune system to direct downstream immune responses. Here, we have sought to use DCs ex vivo to identify immunogenic products from heat-killed B. pseudomallei. Using practical volumes of fresh human donor blood, we show that heat-killed B. pseudomallei activated and stimulated the expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 from both myeloid and plasmacytoid DCs. Furthermore, B. pseudomallei-pulsed DCs cultured with naïve syngeneic T cells ex vivo, induced the activation and proliferation of the CD4⁺ T-cell population, which was identified by cell surface marker staining using flow cytometry. Thus, both DC subsets are important for driving primary T helper cell responses to B. pseudomallei in healthy individuals and have the potential to be used to identify immunogenic components of B. pseudomallei for future therapies and vaccines. Full article

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15 pages, 2449 KiB

Open AccessArticle

Chlamydia trachomatis Cross-Serovar Protection during Experimental Lung Reinfection in Mice

by Christian Lanfermann, Martin Kohn, Robert Laudeley, Claudia Rheinheimer and Andreas Klos

Vaccines 2021, 9(8), 871; https://doi.org/10.3390/vaccines9080871 - 6 Aug 2021

Cited by 1 | Viewed by 2589

Abstract

Chlamydia trachomatis causes most bacterial sexually transmitted diseases worldwide. Different major outer membrane proteins (MOMPs) define various serovars of this intracellular pathogen: In women, D to L3 can cause urethritis, cervicitis, salpingitis, and oophoritis, and, thus, infertility. Protective immunity might be serovar-specific since [...] Read more.

Chlamydia trachomatis causes most bacterial sexually transmitted diseases worldwide. Different major outer membrane proteins (MOMPs) define various serovars of this intracellular pathogen: In women, D to L3 can cause urethritis, cervicitis, salpingitis, and oophoritis, and, thus, infertility. Protective immunity might be serovar-specific since chlamydial infection does not appear to induce an effective acquired immunity and reinfections occur. A better understanding of induced cross-serovar protection is essential for the selection of suitable antigens in vaccine development. In our mouse lung infection screening model, we evaluated the urogenital serovars D, E, and L2 in this regard. Seven weeks after primary infection or mock-infection, respectively, mice were infected a second time with the identical or one of the other serovars. Body weight and clinical score were monitored for 7 days. Near the peak of the second lung infection, bacterial load, myeloperoxidase, IFN-γ, and TNF-α in lung homogenate, as well as chlamydia-specific IgG levels in blood were determined. Surprisingly, compared with mice that were infected then for the first time, almost independent of the serovar combination used, all acquired parameters of disease were similarly diminished. Our reinfection study suggests that efficient cross-serovar protection could be achieved by a vaccine combining chlamydial antigens that do not include nonconserved MOMP regions. Full article

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