Vaccines

Editorial

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5 pages, 190 KiB

Open AccessEditorial

Advances in Vaccine Development

by Ralph A. Tripp

Vaccines 2021, 9(9), 1036; https://doi.org/10.3390/vaccines9091036 - 18 Sep 2021

Cited by 3 | Viewed by 3448

Abstract

The Special Issue titled “Advances in Vaccine Development” contains articles, reviews, and a perspective on advances in vaccine delivery and expression, nanovaccines, epitopes, proteins and adjuvants, and new vaccine platforms [...] Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

Research

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23 pages, 3742 KiB

Open AccessFeature PaperArticle

Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches

by Rahul Chatterjee, Panchanan Sahoo, Soumya Ranjan Mahapatra, Jyotirmayee Dey, Mrinmoy Ghosh, Gajraj Singh Kushwaha, Namrata Misra, Mrutyunjay Suar, Vishakha Raina and Young-Ok Son

Vaccines 2021, 9(9), 1038; https://doi.org/10.3390/vaccines9091038 - 18 Sep 2021

Cited by 35 | Viewed by 4815

Abstract

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major [...] Read more.

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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13 pages, 1348 KiB

Open AccessArticle

Novel Surrogate Neutralizing Assay Supports Parvovirus B19 Vaccine Development for Children with Sickle Cell Disease

by Rhiannon R. Penkert, Sumana Chandramouli, Philip R. Dormitzer, Ethan C. Settembre, Robert E. Sealy, Susan Wong, Neal S. Young, Yilun Sun, Li Tang, Alyssa Cotton, Jola Dowdy, Randall T. Hayden, Jane S. Hankins and Julia L. Hurwitz

Vaccines 2021, 9(8), 860; https://doi.org/10.3390/vaccines9080860 - 4 Aug 2021

Cited by 3 | Viewed by 2927

Abstract

Children with sickle cell disease (SCD) suffer life-threatening transient aplastic crisis (TAC) when infected with parvovirus B19. In utero, infection of healthy fetuses may result in anemia, hydrops, and death. Unfortunately, although promising vaccine candidates exist, no product has yet been licensed. One [...] Read more.

Children with sickle cell disease (SCD) suffer life-threatening transient aplastic crisis (TAC) when infected with parvovirus B19. In utero, infection of healthy fetuses may result in anemia, hydrops, and death. Unfortunately, although promising vaccine candidates exist, no product has yet been licensed. One barrier to vaccine development has been the lack of a cost-effective, standardized parvovirus B19 neutralization assay. To fill this void, we evaluated the unique region of VP1 (VP1u), which contains prominent targets of neutralizing antibodies. We discovered an antigenic cross-reactivity between VP1 and VP2 that, at first, thwarted the development of a surrogate neutralization assay. We overcame the cross-reactivity by designing a mutated VP1u (VP1uAT) fragment. A new VP1uAT ELISA yielded results well correlated with neutralization (Spearman’s correlation coefficient = 0.581; p = 0.001), superior to results from a standard clinical diagnostic ELISA or an ELISA with virus-like particles. Virus-specific antibodies from children with TAC, measured by the VP1uAT and neutralization assays, but not other assays, gradually increased from days 0 to 120 post-hospitalization. We propose that this novel and technically simple VP1uAT ELISA might now serve as a surrogate for the neutralization assay to support rapid development of a parvovirus B19 vaccine. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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13 pages, 1325 KiB

Open AccessArticle

Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

by Megan M. Dunagan, Kala Hardy and Toru Takimoto

Vaccines 2021, 9(6), 629; https://doi.org/10.3390/vaccines9060629 - 10 Jun 2021

Cited by 9 | Viewed by 3099

Abstract

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X [...] Read more.

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4⁺ and CD8⁺ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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17 pages, 4463 KiB

Open AccessArticle

African Trypanosomosis Obliterates DTPa Vaccine-Induced Functional Memory So That Post-Treatment Bordetella pertussis Challenge Fails to Trigger a Protective Recall Response

by Magdalena Radwanska, Hang Thi Thu Nguyen and Stefan Magez

Vaccines 2021, 9(6), 603; https://doi.org/10.3390/vaccines9060603 - 4 Jun 2021

Cited by 7 | Viewed by 2770

Abstract

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination is considered the only sustainable method for global trypanosomosis control. Unfortunately, no single field applicable vaccine solution has been successful so far. The active destruction of the host’s adaptive immune system [...] Read more.

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination is considered the only sustainable method for global trypanosomosis control. Unfortunately, no single field applicable vaccine solution has been successful so far. The active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here, we show that Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and a diminazene diaceturate anti-parasite treatment scheme, our results demonstrate that while the latter ensured full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-B. pertussis vaccine recall response. The DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-B. pertussis antibody ratio in favor of IgG2a, and a striking impact on all of the spleen immune cell populations. Interestingly, an increased plasma IFNγ level in DTPa-vaccinated trypanosome-infected mice coincided with a temporary antibody-independent improvement in early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome-inflicted immune damage is not restored by successful anti-parasite treatment. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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15 pages, 1873 KiB

Open AccessArticle

The C-Terminal Domain of Nef^mut Is Dispensable for the CD8⁺ T Cell Immunogenicity of In Vivo Engineered Extracellular Vesicles

by Chiara Chiozzini, Francesco Manfredi, Flavia Ferrantelli, Patrizia Leone, Andrea Giovannelli, Eleonora Olivetta and Maurizio Federico

Vaccines 2021, 9(4), 373; https://doi.org/10.3390/vaccines9040373 - 12 Apr 2021

Cited by 5 | Viewed by 3283

Abstract

Intramuscular injection of DNA vectors expressing the extracellular vesicle (EV)-anchoring protein Nef^mut fused at its C-terminus to viral and tumor antigens elicit a potent, effective, and anti-tolerogenic CD8⁺ T cell immunity against the heterologous antigen. The immune response is induced through [...] Read more.

Intramuscular injection of DNA vectors expressing the extracellular vesicle (EV)-anchoring protein Nef^mut fused at its C-terminus to viral and tumor antigens elicit a potent, effective, and anti-tolerogenic CD8⁺ T cell immunity against the heterologous antigen. The immune response is induced through the production of EVs incorporating Nef^mut-derivatives released by muscle cells. In the perspective of a possible translation into the clinic of the Nef^mut-based vaccine platform, we aimed at increasing its safety profile by identifying the minimal part of Nef^mut retaining the EV-anchoring protein property. We found that a C-terminal deletion of 29-amino acids did not affect the ability of Nef^mut to associate with EVs. The EV-anchoring function was also preserved when antigens from both HPV16 (i.e., E6 and E7) and SARS-CoV-2 (i.e., S1 and S2) were fused to its C-terminus. Most important, the Nef^mut C-terminal deletion did not affect levels, quality, and diffusion at distal sites of the antigen-specific CD8⁺ T immunity. We concluded that the C-terminal Nef^mut truncation does not influence stability, EV-anchoring, and CD8⁺ T cell immunogenicity of the fused antigen. Hence, the C-terminal deleted Nef^mut may represent a safer alternative to the full-length isoform for vaccines in humans. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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Review

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27 pages, 2917 KiB

Open AccessReview

An Overview of Influenza Viruses and Vaccines

by Rina Fajri Nuwarda, Abdulsalam Abdullah Alharbi and Veysel Kayser

Vaccines 2021, 9(9), 1032; https://doi.org/10.3390/vaccines9091032 - 17 Sep 2021

Cited by 81 | Viewed by 23153

Abstract

Influenza remains one of the major public health concerns because it causes annual epidemics and can potentially instigate a global pandemic. Numerous countermeasures, including vaccines and antiviral treatments, are in use against seasonal influenza infection; however, their effectiveness has always been discussed due [...] Read more.

Influenza remains one of the major public health concerns because it causes annual epidemics and can potentially instigate a global pandemic. Numerous countermeasures, including vaccines and antiviral treatments, are in use against seasonal influenza infection; however, their effectiveness has always been discussed due to the ongoing resistance to antivirals and relatively low and unpredictable efficiency of influenza vaccines compared to other vaccines. The growing interest in vaccines as a promising approach to prevent and control influenza may provide alternative vaccine development options with potentially increased efficiency. In addition to currently available inactivated, live-attenuated, and recombinant influenza vaccines on the market, novel platforms such as virus-like particles (VLPs) and nanoparticles, and new vaccine formulations are presently being explored. These platforms provide the opportunity to design influenza vaccines with improved properties to maximize quality, efficacy, and safety. The influenza vaccine manufacturing process is also moving forward with advancements relating to egg- and cell-based production, purification processes, and studies into the physicochemical attributes and vaccine degradation pathways. These will contribute to the design of more stable, optimized vaccine formulations guided by contemporary analytical testing methods and via the implementation of the latest advances in the field. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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31 pages, 1771 KiB

Open AccessReview

The Promise and Challenges of Cyclic Dinucleotides as Molecular Adjuvants for Vaccine Development

by Hongbin Yan and Wangxue Chen

Vaccines 2021, 9(8), 917; https://doi.org/10.3390/vaccines9080917 - 17 Aug 2021

Cited by 21 | Viewed by 4470

Abstract

Cyclic dinucleotides (CDNs), originally discovered as bacterial second messengers, play critical roles in bacterial signal transduction, cellular processes, biofilm formation, and virulence. The finding that CDNs can trigger the innate immune response in eukaryotic cells through the stimulator of interferon genes (STING) signalling [...] Read more.

Cyclic dinucleotides (CDNs), originally discovered as bacterial second messengers, play critical roles in bacterial signal transduction, cellular processes, biofilm formation, and virulence. The finding that CDNs can trigger the innate immune response in eukaryotic cells through the stimulator of interferon genes (STING) signalling pathway has prompted the extensive research and development of CDNs as potential immunostimulators and novel molecular adjuvants for induction of systemic and mucosal innate and adaptive immune responses. In this review, we summarize the chemical structure, biosynthesis regulation, and the role of CDNs in enhancing the crosstalk between host innate and adaptive immune responses. We also discuss the strategies to improve the efficient delivery of CDNs and the recent advance and future challenges in the development of CDNs as potential adjuvants in prophylactic vaccines against infectious diseases and in therapeutic vaccines against cancers. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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17 pages, 1831 KiB

Open AccessReview

Antigen Presentation of mRNA-Based and Virus-Vectored SARS-CoV-2 Vaccines

by Ger T. Rijkers, Nynke Weterings, Andres Obregon-Henao, Michaëla Lepolder, Taru S. Dutt, Frans J. van Overveld and Marcela Henao-Tamayo

Vaccines 2021, 9(8), 848; https://doi.org/10.3390/vaccines9080848 - 3 Aug 2021

Cited by 65 | Viewed by 16721

Abstract

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale [...] Read more.

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of viral Spike S1 protein encoding mRNA incorporated in a lipid nanoparticle and stabilized by polyethylene glycol (PEG). The mRNA vaccines are novel in many respects, including cellular uptake and the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences, encoding the SARS-CoV-2 Spike protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to the induction of virus-neutralizing antibodies and cytotoxic T-lymphocytes, will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. The mRNA-based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG and potential presentation in the context of CD1 will be discussed. Adenovirus vector-based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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19 pages, 334 KiB

Open AccessReview

Using Adjuvants to Drive T Cell Responses for Next-Generation Infectious Disease Vaccines

by Rekha R. Rapaka, Alan S. Cross and Monica A. McArthur

Vaccines 2021, 9(8), 820; https://doi.org/10.3390/vaccines9080820 - 24 Jul 2021

Cited by 22 | Viewed by 4354

Abstract

Using adjuvants to drive features of T cell responses to vaccine antigens is an important technological challenge in the design of new and improved vaccines against infections. Properties such as T helper cell function, T cell memory, and CD8+ T cell cytotoxicity may [...] Read more.

Using adjuvants to drive features of T cell responses to vaccine antigens is an important technological challenge in the design of new and improved vaccines against infections. Properties such as T helper cell function, T cell memory, and CD8+ T cell cytotoxicity may play critical roles in optimal and long-lived immunity through vaccination. Directly manipulating specific immune activation or antigen delivery pathways with adjuvants may selectively augment desired T cell responses in vaccination and may improve the effectiveness and durability of vaccine responses in humans. In this review we outline recently studied adjuvants in their potential for antigen presenting cell and T cell programming during vaccination, with an emphasis on what has been observed in studies in humans as available. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

17 pages, 1651 KiB

Open AccessReview

Next-Generation Bioinformatics Approaches and Resources for Coronavirus Vaccine Discovery and Development—A Perspective Review

by Rahul Chatterjee, Mrinmoy Ghosh, Susrita Sahoo, Santwana Padhi, Namrata Misra, Visakha Raina, Mrutyunjay Suar and Young-Ok Son

Vaccines 2021, 9(8), 812; https://doi.org/10.3390/vaccines9080812 - 22 Jul 2021

Cited by 15 | Viewed by 6719

Abstract

COVID-19 is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To fight this pandemic, which has caused a massive death toll around the globe, researchers are putting efforts into developing an effective vaccine against the pathogen. As genome sequencing [...] Read more.

COVID-19 is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To fight this pandemic, which has caused a massive death toll around the globe, researchers are putting efforts into developing an effective vaccine against the pathogen. As genome sequencing projects for several coronavirus strains have been completed, a detailed investigation of the functions of the proteins and their 3D structures has gained increasing attention. These high throughput data are a valuable resource for accelerating the emerging field of immuno-informatics, which is primarily aimed toward the identification of potential antigenic epitopes in viral proteins that can be targeted for the development of a vaccine construct eliciting a high immune response. Bioinformatics platforms and various computational tools and databases are also essential for the identification of promising vaccine targets making the best use of genomic resources, for further experimental validation. The present review focuses on the various stages of the vaccine development process and the vaccines available for COVID-19. Additionally, recent advances in genomic platforms and publicly available bioinformatics resources in coronavirus vaccine discovery together with related immunoinformatics databases and advances in technology are discussed. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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11 pages, 284 KiB

Open AccessReview

Advances in Human Norovirus Vaccine Research

by Mudan Zhang, Ming Fu and Qinxue Hu

Vaccines 2021, 9(7), 732; https://doi.org/10.3390/vaccines9070732 - 2 Jul 2021

Cited by 37 | Viewed by 5215

Abstract

Human norovirus (HuNoV) is the leading cause of acute gastroenteritis (AGE) worldwide, which is highly stable and contagious, with a few virus particles being sufficient to establish infection. Although the World Health Organization in 2016 stated that it should be an absolute priority [...] Read more.

Human norovirus (HuNoV) is the leading cause of acute gastroenteritis (AGE) worldwide, which is highly stable and contagious, with a few virus particles being sufficient to establish infection. Although the World Health Organization in 2016 stated that it should be an absolute priority to develop a HuNoV vaccine, unfortunately, there is currently no licensed HuNoV vaccine available. The major barrier to the development of an effective HuNoV vaccine is the lack of a robust and reproducible in vitro cultivation system. To develop a HuNoV vaccine, HuNoV immunogen alone or in combination with other viral immunogens have been designed to assess whether they can simultaneously induce protective immune responses against different viruses. Additionally, monovalent and multivalent vaccines from different HuNoV genotypes, including GI and GII HuNoV virus-like particles (VLPs), have been assessed in order to induce broad protection. Although there are several HuNoV vaccine candidates based on VLPs that are being tested in clinical trials, the challenges to develop effective HuNoV vaccines remain largely unresolved. In this review, we summarize the advances of the HuNoV cultivation system and HuNoV vaccine research and discuss current challenges and future perspectives in HuNoV vaccine development. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

28 pages, 1100 KiB

Open AccessReview

Resistance to Ticks and the Path to Anti-Tick and Transmission Blocking Vaccines

by Jolieke G. van Oosterwijk and Stephen K. Wikel

Vaccines 2021, 9(7), 725; https://doi.org/10.3390/vaccines9070725 - 2 Jul 2021

Cited by 25 | Viewed by 5867

Abstract

The medical and veterinary public health importance of ticks and tick-borne pathogens is increasing due to the expansion of the geographic ranges of both ticks and pathogens, increasing tick populations, growing incidence of tick-borne diseases, emerging tick transmitted pathogens, and continued challenges of [...] Read more.

The medical and veterinary public health importance of ticks and tick-borne pathogens is increasing due to the expansion of the geographic ranges of both ticks and pathogens, increasing tick populations, growing incidence of tick-borne diseases, emerging tick transmitted pathogens, and continued challenges of achieving effective and sustained tick control. The past decades show an increasing interest in the immune-mediated control of tick infestations and pathogen transmission through the use of vaccines. Bovine tick resistance induced by repeated infestations was reported over a century ago. This review addresses the phenomena and immunological underpinning of resistance to tick infestation by livestock and laboratory animals; the scope of tick countermeasures to host immune defenses; and the impact of genomics, functional genomics, and proteomics on dissecting complex tick–host–pathogen interactions. From early studies utilizing tick tissue extracts to salivary gland derived molecules and components of physiologically important pathways in tick gut and other tissues, an increased understanding of these relationships, over time, impacted the evolution of anti-tick vaccine antigen selection. Novel antigens continue to emerge, including increased interest in the tick microbiome. Anti-tick and transmission blocking vaccines targeting pathogen reservoirs have the potential to disrupt enzootic cycles and reduce human, companion, domestic animal, and wildlife exposure to infected ticks. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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19 pages, 1168 KiB

Open AccessReview

Immunization and Immunotherapy Approaches against Pseudomonas aeruginosa and Burkholderia cepacia Complex Infections

by Sílvia A. Sousa, António M. M. Seixas, Joana M. M. Marques and Jorge H. Leitão

Vaccines 2021, 9(6), 670; https://doi.org/10.3390/vaccines9060670 - 18 Jun 2021

Cited by 18 | Viewed by 5644

Abstract

Human infections caused by the opportunist pathogens Burkholderia cepacia complex and Pseudomonas aeruginosa are of particular concern due to their severity, their multiple antibiotic resistance, and the limited eradication efficiency of the current available treatments. New therapeutic options have been pursued, being vaccination [...] Read more.

Human infections caused by the opportunist pathogens Burkholderia cepacia complex and Pseudomonas aeruginosa are of particular concern due to their severity, their multiple antibiotic resistance, and the limited eradication efficiency of the current available treatments. New therapeutic options have been pursued, being vaccination strategies to prevent or limit these infections as a rational approach to tackle these infections. In this review, immunization and immunotherapy approaches currently available and under study against these bacterial pathogens is reviewed. Ongoing active and passive immunization clinical trials against P. aeruginosa infections is also reviewed. Novel identified bacterial targets and their possible exploitation for the development of immunization and immunotherapy strategies against P. aeruginosa and B. cepacia complex and infections are also presented and discussed. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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15 pages, 1090 KiB

Open AccessReview

Considerations for a Respiratory Syncytial Virus Vaccine Targeting an Elderly Population

by Laura M. Stephens and Steven M. Varga

Vaccines 2021, 9(6), 624; https://doi.org/10.3390/vaccines9060624 - 9 Jun 2021

Cited by 33 | Viewed by 6404

Abstract

Respiratory syncytial virus (RSV) is most commonly associated with acute lower respiratory tract infections in infants and children. However, RSV also causes a high disease burden in the elderly that is often under recognized. Adults >65 years of age account for an estimated [...] Read more.

Respiratory syncytial virus (RSV) is most commonly associated with acute lower respiratory tract infections in infants and children. However, RSV also causes a high disease burden in the elderly that is often under recognized. Adults >65 years of age account for an estimated 80,000 RSV-associated hospitalizations and 14,000 deaths in the United States annually. RSV infection in aged individuals can result in more severe disease symptoms including pneumonia and bronchiolitis. Given the large disease burden caused by RSV in the aged, this population remains an important target for vaccine development. Aging results in lowered immune responsiveness characterized by impairments in both innate and adaptive immunity. This immune senescence poses a challenge when developing a vaccine targeting elderly individuals. An RSV vaccine tailored towards an elderly population will need to maximize the immune response elicited in order to overcome age-related defects in the immune system. In this article, we review the hurdles that must be overcome to successfully develop an RSV vaccine for use in the elderly, and discuss the vaccine candidates currently being tested in this highly susceptible population. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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18 pages, 814 KiB

Open AccessReview

Nano-Microparticle Platforms in Developing Next-Generation Vaccines

by Giuseppe Cappellano, Hugo Abreu, Chiara Casale, Umberto Dianzani and Annalisa Chiocchetti

Vaccines 2021, 9(6), 606; https://doi.org/10.3390/vaccines9060606 - 5 Jun 2021

Cited by 37 | Viewed by 5488

Abstract

The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8⁺ T-cell response. [...] Read more.

The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8⁺ T-cell response. In contrast, next-generation nano/microparticle-based vaccines offer several advantages over traditional ones because they can induce a more potent CD8⁺ T-cell response and, at the same time, are ideal carriers for proteins, adjuvants, and nucleic acids. The fact that these nanocarriers can be loaded with molecules able to modulate the immune response by inducing different effector functions and regulatory activities makes them ideal tools for inverse vaccination, whose goal is to shut down the immune response in autoimmune diseases. Poly (lactic-co-glycolic acid) (PLGA) and liposomes are biocompatible materials approved by the Food and Drug Administration (FDA) for clinical use and are, therefore, suitable for nanoparticle-based vaccines. Recently, another candidate platform for innovative vaccines based on extracellular vesicles (EVs) has been shown to efficiently co-deliver antigens and adjuvants. This review will discuss the potential use of PLGA-NPs, liposomes, and EVs as carriers of peptides, adjuvants, mRNA, and DNA for the development of next-generation vaccines against endemic and emerging viruses in light of the recent COVID-19 pandemic. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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15 pages, 608 KiB

Open AccessReview

Intranasal Vaccine Delivery Technology for Respiratory Tract Disease Application with a Special Emphasis on Pneumococcal Disease

by William Walkowski, Justin Bassett, Manmeet Bhalla, Blaine A. Pfeifer and Elsa N. Bou Ghanem

Vaccines 2021, 9(6), 589; https://doi.org/10.3390/vaccines9060589 - 2 Jun 2021

Cited by 6 | Viewed by 9470

Abstract

This mini-review will cover recent trends in intranasal (IN) vaccine delivery as it relates to applications for respiratory tract diseases. The logic and rationale for IN vaccine delivery will be compared to methods and applications accompanying this particular administration route. In addition, we [...] Read more.

This mini-review will cover recent trends in intranasal (IN) vaccine delivery as it relates to applications for respiratory tract diseases. The logic and rationale for IN vaccine delivery will be compared to methods and applications accompanying this particular administration route. In addition, we will focus extended discussion on the potential role of IN vaccination in the context of respiratory tract diseases, with a special emphasis on pneumococcal disease. Here, elements of this disease, including its prevalence and impact upon the elderly population, will be viewed from the standpoint of improving health outcomes through vaccine design and delivery technology and how IN administration can play a role in such efforts. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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25 pages, 1526 KiB

Open AccessReview

Mapping Global Prevalence of Acinetobacter baumannii and Recent Vaccine Development to Tackle It

by Chaoying Ma and Siobhán McClean

Vaccines 2021, 9(6), 570; https://doi.org/10.3390/vaccines9060570 - 1 Jun 2021

Cited by 56 | Viewed by 8438

Abstract

Acinetobacter baumannii is a leading cause of nosocomial infections that severely threaten public health. The formidable adaptability and resistance of this opportunistic pathogen have hampered the development of antimicrobial therapies which consequently leads to very limited treatment options. We mapped the global prevalence [...] Read more.

Acinetobacter baumannii is a leading cause of nosocomial infections that severely threaten public health. The formidable adaptability and resistance of this opportunistic pathogen have hampered the development of antimicrobial therapies which consequently leads to very limited treatment options. We mapped the global prevalence of multidrug-resistant A. baumannii and showed that carbapenem-resistant A. baumannii is widespread throughout Asia and the Americas. Moreover, when antimicrobial resistance rates of Acinetobacter spp. exceed a threshold level, the proportion of A. baumannii isolates from clinical samples surges. Therefore, vaccines represent a realistic alternative strategy to tackle this pathogen. Research into anti-A. baumannii vaccines have enhanced in the past decade and multiple antigens have been investigated preclinically with varying results. This review summarises the current knowledge of virulence factors relating to A. baumannii–host interactions and its implication in vaccine design, with a view to understanding the current state of A. baumannii vaccine development and the direction of future efforts. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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24 pages, 5279 KiB

Open AccessReview

Chemical Conjugation Strategies for the Development of Protein-Based Subunit Nanovaccines

by Lantian Lu, Viet Tram Duong, Ahmed O. Shalash, Mariusz Skwarczynski and Istvan Toth

Vaccines 2021, 9(6), 563; https://doi.org/10.3390/vaccines9060563 - 28 May 2021

Cited by 62 | Viewed by 8816

Abstract

The production of subunit nanovaccines relies heavily on the development of a vaccine delivery system that is safe and efficient at delivering antigens to the target site. Nanoparticles have been extensively investigated for vaccine delivery over the years, as they often possess self-adjuvanting [...] Read more.

The production of subunit nanovaccines relies heavily on the development of a vaccine delivery system that is safe and efficient at delivering antigens to the target site. Nanoparticles have been extensively investigated for vaccine delivery over the years, as they often possess self-adjuvanting properties. The conjugation of antigens to nanoparticles by covalent bonds ensures co-delivery of these components to the same subset of immune cells in order to trigger the desired immune responses. Herein, we review covalent conjugation strategies for grafting protein or peptide antigens onto other molecules or nanoparticles to obtain subunit nanovaccines. We also discuss the advantages of chemical conjugation in developing these vaccines. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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20 pages, 10685 KiB

Open AccessReview

Recent Advances and Future Perspectives in Polymer-Based Nanovaccines

by Natassa Pippa, Maria Gazouli and Stergios Pispas

Vaccines 2021, 9(6), 558; https://doi.org/10.3390/vaccines9060558 - 26 May 2021

Cited by 43 | Viewed by 5898

Abstract

Vaccination is the most valuable and cost-effective health measure to prevent and control the spread of infectious diseases. A significant number of infectious diseases and chronic disorders are still not preventable by existing vaccination schemes; therefore, new-generation vaccines are needed. Novel technologies such [...] Read more.

Vaccination is the most valuable and cost-effective health measure to prevent and control the spread of infectious diseases. A significant number of infectious diseases and chronic disorders are still not preventable by existing vaccination schemes; therefore, new-generation vaccines are needed. Novel technologies such as nanoparticulate systems and adjuvants can enable safe and effective vaccines for difficult target populations such as newborns, elderly, and the immune-compromised. More recently, polymer-based particles have found application as vaccine platforms and vaccine adjuvants due to their ability to prevent antigen degradation and clearance, coupled with enhanced uptake by professional antigen-presenting cells (APCs). Polymeric nanoparticles have been applied in vaccine delivery, showing significant adjuvant effects as they can easily be taken up by APCs. In other words, polymer-based systems offer a lot of advantages, including versatility and flexibility in the design process, the ability to incorporate a range of immunomodulators/antigens, mimicking infection in different ways, and acting as a depot, thereby persisting long enough to generate adaptive immune responses. The aim of this review is to summarize the properties, the characteristics, the added value, and the limitations of the polymer-based nanovaccines, as well as the process of their development by the pharmaceutical industry. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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26 pages, 661 KiB

Open AccessReview

Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice

by Sara Scarpini, Francesca Morigi, Ludovica Betti, Arianna Dondi, Carlotta Biagi and Marcello Lanari

Vaccines 2021, 9(6), 551; https://doi.org/10.3390/vaccines9060551 - 25 May 2021

Cited by 51 | Viewed by 7026

Abstract

Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymptomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive [...] Read more.

Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymptomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive development and represents the leading cause of non-genetic sensorineural hearing loss. Moreover, even if hCMV mostly causes asymptomatic or pauci-symptomatic infections in immunocompetent hosts, it may lead to severe and life-threatening disease in immunocompromised patients. Since immunity reduces the severity of disease, in the last years, the development of an effective and safe hCMV vaccine has been of great interest to pharmacologic researchers. Both hCMV live vaccines—e.g., live-attenuated, chimeric, viral-based—and non-living ones—subunit, RNA-based, virus-like particles, plasmid-based DNA—have been investigated. Encouraging data are emerging from clinical trials, but a hCMV vaccine has not been licensed yet. Major difficulties in the development of a satisfactory vaccine include hCMV’s capacity to evade the immune response, unclear immune correlates for protection, low number of available animal models, and insufficient general awareness. Moreover, there is a need to determine which may be the best target populations for vaccine administration. The aim of the present paper is to examine the status of hCMV vaccines undergoing clinical trials and understand barriers limiting their development. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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16 pages, 573 KiB

Open AccessReview

Advances in Toxoplasma gondii Vaccines: Current Strategies and Challenges for Vaccine Development

by Ki-Back Chu and Fu-Shi Quan

Vaccines 2021, 9(5), 413; https://doi.org/10.3390/vaccines9050413 - 21 Apr 2021

Cited by 44 | Viewed by 8175

Abstract

Toxoplasmosis, caused by the apicomplexan parasite Toxoplasma gondii, is one of the most damaging parasite-borne zoonotic diseases of global importance. While approximately one-third of the entire world’s population is estimated to be infected with T. gondii, an effective vaccine for human [...] Read more.

Toxoplasmosis, caused by the apicomplexan parasite Toxoplasma gondii, is one of the most damaging parasite-borne zoonotic diseases of global importance. While approximately one-third of the entire world’s population is estimated to be infected with T. gondii, an effective vaccine for human use remains unavailable. Global efforts in pursuit of developing a T. gondii vaccine have been ongoing for decades, and novel innovative approaches have been introduced to aid this process. A wide array of vaccination strategies have been conducted to date including, but not limited to, nucleic acids, protein subunits, attenuated vaccines, and nanoparticles, which have been assessed in rodents with promising results. Yet, translation of these in vivo results into clinical studies remains a major obstacle that needs to be overcome. In this review, we will aim to summarize the current advances in T. gondii vaccine strategies and address the challenges hindering vaccine development. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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19 pages, 2551 KiB

Open AccessReview

Mechanisms of Hepatitis C Virus Escape from Vaccine-Relevant Neutralizing Antibodies

by Rodrigo Velázquez-Moctezuma, Elias H. Augestad, Matteo Castelli, Christina Holmboe Olesen, Nicola Clementi, Massimo Clementi, Nicasio Mancini and Jannick Prentoe

Vaccines 2021, 9(3), 291; https://doi.org/10.3390/vaccines9030291 - 20 Mar 2021

Cited by 10 | Viewed by 4542

Abstract

Hepatitis C virus (HCV) is a major causative agent of acute and chronic hepatitis. It is estimated that 400,000 people die every year from chronic HCV infection, mostly from severe liver-related diseases such as cirrhosis and liver cancer. Although HCV was discovered more [...] Read more.

Hepatitis C virus (HCV) is a major causative agent of acute and chronic hepatitis. It is estimated that 400,000 people die every year from chronic HCV infection, mostly from severe liver-related diseases such as cirrhosis and liver cancer. Although HCV was discovered more than 30 years ago, an efficient prophylactic vaccine is still missing. The HCV glycoprotein complex, E1/E2, is the principal target of neutralizing antibodies (NAbs) and, thus, is an attractive antigen for B-cell vaccine design. However, the high genetic variability of the virus necessitates the identification of conserved epitopes. Moreover, the high intrinsic mutational capacity of HCV allows the virus to continually escape broadly NAbs (bNAbs), which is likely to cause issues with vaccine-resistant variants. Several studies have assessed the barrier-to-resistance of vaccine-relevant bNAbs in vivo and in vitro. Interestingly, recent studies have suggested that escape substitutions can confer antibody resistance not only by direct modification of the epitope but indirectly through allosteric effects, which can be grouped based on the breadth of these effects on antibody susceptibility. In this review, we summarize the current understanding of HCV-specific NAbs, with a special focus on vaccine-relevant bNAbs and their targets. We highlight antibody escape studies pointing out the different methodologies and the escape mutations identified thus far. Finally, we analyze the antibody escape mechanisms of envelope protein escape substitutions and polymorphisms according to the most recent evidence in the HCV field. The accumulated knowledge in identifying bNAb epitopes as well as assessing barriers to resistance and elucidating relevant escape mechanisms may prove critical in the successful development of an HCV B-cell vaccine. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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25 pages, 1777 KiB

Open AccessReview

Immunity against Lagovirus europaeus and the Impact of the Immunological Studies on Vaccination

by Claudia Müller, Rafał Hrynkiewicz, Dominika Bębnowska, Jaime Maldonado, Massimiliano Baratelli, Bernd Köllner and Paulina Niedźwiedzka-Rystwej

Vaccines 2021, 9(3), 255; https://doi.org/10.3390/vaccines9030255 - 13 Mar 2021

Cited by 22 | Viewed by 3939

Abstract

In the early 1980s, a highly contagious viral hemorrhagic fever in rabbits (Oryctolagus cuniculus) emerged, causing a very high rate of mortality in these animals. Since the initial occurrence of the rabbit hemorrhagic disease virus (RHDV), several hundred million rabbits have [...] Read more.

In the early 1980s, a highly contagious viral hemorrhagic fever in rabbits (Oryctolagus cuniculus) emerged, causing a very high rate of mortality in these animals. Since the initial occurrence of the rabbit hemorrhagic disease virus (RHDV), several hundred million rabbits have died after infection. The emergence of genetically-different virus variants (RHDV GI.1 and GI.2) indicated the very high variability of RHDV. Moreover, with these variants, the host range broadened to hare species (Lepus). The circulation of RHDV genotypes displays different virulences and a limited induction of cross-protective immunity. Interestingly, juvenile rabbits (<9 weeks of age) with an immature immune system display a general resistance to RHDV GI.1, and a limited resistance to RHDV GI.2 strains, whereas less than 3% of adult rabbits survive an infection by either RHDV GI.1. or GI.2. Several not-yet fully understood phenomena characterize the RHD. A very low infection dose followed by an extremely rapid viral replication could be simplified to the induction of a disseminated intravascular coagulopathy (DIC), a severe loss of lymphocytes—especially T-cells—and death within 36 to 72 h post infection. On the other hand, in animals surviving the infection or after vaccination, very high titers of RHDV-neutralizing antibodies were induced. Several studies have been conducted in order to deepen the knowledge about the virus’ genetics, epidemiology, RHDV-induced pathology, and the anti-RHDV immune responses of rabbits in order to understand the phenomenon of the juvenile resistance to this virus. Moreover, several approaches have been used to produce efficient vaccines in order to prevent an infection with RHDV. In this review, we discuss the current knowledge about anti-RHDV resistance and immunity, RHDV vaccination, and the further need to establish rationally-based RHDV vaccines. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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14 pages, 1034 KiB

Open AccessReview

A COVID-19 Vaccine: Big Strides Come with Big Challenges

by Juanita Mellet and Michael S. Pepper

Vaccines 2021, 9(1), 39; https://doi.org/10.3390/vaccines9010039 - 11 Jan 2021

Cited by 72 | Viewed by 19780

Abstract

As of 8 January 2021, there were 86,749,940 confirmed coronavirus disease 2019 (COVID-19) cases and 1,890,342 COVID-19-related deaths worldwide, as reported by the World Health Organization (WHO). In order to address the COVID-19 pandemic by limiting transmission, an intense global effort is underway [...] Read more.

As of 8 January 2021, there were 86,749,940 confirmed coronavirus disease 2019 (COVID-19) cases and 1,890,342 COVID-19-related deaths worldwide, as reported by the World Health Organization (WHO). In order to address the COVID-19 pandemic by limiting transmission, an intense global effort is underway to develop a vaccine against SARS-CoV-2. The development of a safe and effective vaccine usually requires several years of pre-clinical and clinical stages of evaluation and requires strict regulatory approvals before it can be manufactured in bulk and distributed. Since the global impact of COVID-19 is unprecedented in the modern era, the development and testing of a new vaccine are being expedited. Given the high-level of attrition during vaccine development, simultaneous testing of multiple candidates increases the probability of finding one that is effective. Over 200 vaccines are currently in development, with over 60 candidate vaccines being tested in clinical trials. These make use of various platforms and are at different stages of development. This review discusses the different phases of vaccine development and the various platforms in use for candidate COVID-19 vaccines, including their progress to date. The potential challenges once a vaccine becomes available are also addressed. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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13 pages, 261 KiB

Open AccessReview

Navigating the Quagmire: Comparison and Interpretation of COVID-19 Vaccine Phase 1/2 Clinical Trials

by Luca Tudor Giurgea and Matthew James Memoli

Vaccines 2020, 8(4), 746; https://doi.org/10.3390/vaccines8040746 - 9 Dec 2020

Cited by 5 | Viewed by 8995

Abstract

Vaccines against Coronavirus Disease 2019 Originated-19) have been developed with unprecedented rapidity, many utilizing novel strategies. As of November 2020, a series of publications have outlined the results of phase 1/2 studies of nine different vaccines planned to move forward to phase 3 [...] Read more.

Vaccines against Coronavirus Disease 2019 Originated-19) have been developed with unprecedented rapidity, many utilizing novel strategies. As of November 2020, a series of publications have outlined the results of phase 1/2 studies of nine different vaccines planned to move forward to phase 3 trials. The results are encouraging, demonstrating a paucity of severe or serious adverse events and robust induction of antibody titers. Determination of the vaccine candidates with the highest protective efficacy and best adverse event profiles will be essential in refining public health strategies. However, differences in study design and reporting of data make comparisons of existing phase 1/2 studies difficult. With respect to safety, studies have variable follow-up times and may use different definitions for adverse events. Immunogenicity outcomes are even more inconsistent, with variations in timepoints and critical differences in the types of antibodies studied as well as methodological differences in assays. Furthermore, the correlates of protection in COVID-19 are not known. Harmonization of phase 3 trial designs and use of objective and meaningful clinical outcomes will be crucial in streamlining future global responses to the pandemic. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

34 pages, 319 KiB

Open AccessReview

Current State and Challenges in Developing Respiratory Syncytial Virus Vaccines

by Carlotta Biagi, Arianna Dondi, Sara Scarpini, Alessandro Rocca, Silvia Vandini, Giulia Poletti and Marcello Lanari

Vaccines 2020, 8(4), 672; https://doi.org/10.3390/vaccines8040672 - 11 Nov 2020

Cited by 45 | Viewed by 6277

Abstract

Respiratory syncytial virus (RSV) is the main cause of acute respiratory tract infections in infants and it also induces significant disease in the elderly. The clinical course may be severe, especially in high-risk populations (infants and elderly), with a large number of deaths [...] Read more.

Respiratory syncytial virus (RSV) is the main cause of acute respiratory tract infections in infants and it also induces significant disease in the elderly. The clinical course may be severe, especially in high-risk populations (infants and elderly), with a large number of deaths in developing countries and of intensive care hospitalizations worldwide. To date, prevention strategies against RSV infection is based on hygienic measures and passive immunization with humanized monoclonal antibodies, limited to selected high-risk children due to their high costs. The development of a safe and effective vaccine is a global health need and an important objective of research in this field. A growing number of RSV vaccine candidates in different formats (particle-based vaccines, vector-based vaccines, subunit vaccines and live-attenuated vaccines) are being developed and are now at different stages, many of them already being in the clinical stage. While waiting for commercially available safe and effective vaccines, immune prophylaxis in selected groups of high-risk populations is still mandatory. This review summarizes the state-of-the-art of the RSV vaccine research and its implications for clinical practice, focusing on the characteristics of the vaccines that reached the clinical stage of development. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

16 pages, 797 KiB

Open AccessReview

The Interplay between Immunosenescence and Microbiota in the Efficacy of Vaccines

by Rossella Cianci, Laura Franza, Maria Grazia Massaro, Raffaele Borriello, Francesco De Vito and Giovanni Gambassi

Vaccines 2020, 8(4), 636; https://doi.org/10.3390/vaccines8040636 - 2 Nov 2020

Cited by 20 | Viewed by 5550

Abstract

Vaccinations are among the most effective medical procedures and have had an incredible impact on almost everyone’s life. One of the populations that can benefit the most from them are elderly people. Unfortunately, in this group, vaccines are less effective than in other [...] Read more.

Vaccinations are among the most effective medical procedures and have had an incredible impact on almost everyone’s life. One of the populations that can benefit the most from them are elderly people. Unfortunately, in this group, vaccines are less effective than in other groups, due to immunosenescence. The immune system ages like the whole body and becomes less effective in responding to infections and vaccinations. At the same time, immunosenescence also favors an inflammatory microenvironment, which is linked to many conditions typical of the geriatrics population. The microbiota is one of the key actors in modulating the immune response and, in this review, we discuss the current evidence on the role of microbiota in regulating the immune response to vaccines, particularly in elderly people. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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13 pages, 256 KiB

Open AccessReview

An Overview of the Development of New Vaccines for Tuberculosis

by E. Whitlow, A. S. Mustafa and S. N. M. Hanif

Vaccines 2020, 8(4), 586; https://doi.org/10.3390/vaccines8040586 - 5 Oct 2020

Cited by 38 | Viewed by 5174

Abstract

Currently, there is only one licensed vaccine against tuberculosis (TB), the Bacillus Calmette–Guérin (BCG). Despite its protective efficacy against TB in children, BCG has failed to protect adults against pulmonary TB, lacks therapeutic value, and causes complications in immunocompromised individuals. Furthermore, it compromises [...] Read more.

Currently, there is only one licensed vaccine against tuberculosis (TB), the Bacillus Calmette–Guérin (BCG). Despite its protective efficacy against TB in children, BCG has failed to protect adults against pulmonary TB, lacks therapeutic value, and causes complications in immunocompromised individuals. Furthermore, it compromises the use of antigens present in the purified protein derivate of Mycobacterium tuberculosis in the diagnosis of TB. Many approaches, e.g., whole-cell organisms, subunit, and recombinant vaccines are currently being explored for safer and more efficacious TB vaccines than BCG. These approaches have been successful in developing a large number of vaccine candidates included in the TB vaccine pipeline and are at different stages of clinical trials in humans. This paper discusses current vaccination strategies, provides directions for the possible routes towards the development of new TB vaccines and highlights recent findings. The efforts for improved TB vaccines may lead to new licensed vaccines capable of replacing/supplementing BCG and conferring therapeutic value in patients with active/latent TB. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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11 pages, 5750 KiB

Open AccessPerspective

ROS Cocktails as an Adjuvant for Personalized Antitumor Vaccination?

by Ramona Clemen and Sander Bekeschus

Vaccines 2021, 9(5), 527; https://doi.org/10.3390/vaccines9050527 - 19 May 2021

Cited by 11 | Viewed by 3131

Abstract

Cancer is the second leading cause of death worldwide. Today, the critical role of the immune system in tumor control is undisputed. Checkpoint antibody immunotherapy augments existing antitumor T cell activity with durable clinical responses in many tumor entities. Despite the presence of [...] Read more.

Cancer is the second leading cause of death worldwide. Today, the critical role of the immune system in tumor control is undisputed. Checkpoint antibody immunotherapy augments existing antitumor T cell activity with durable clinical responses in many tumor entities. Despite the presence of tumor-associated antigens and neoantigens, many patients have an insufficient repertoires of antitumor T cells. Autologous tumor vaccinations aim at alleviating this defect, but clinical success is modest. Loading tumor material into autologous dendritic cells followed by their laboratory expansion and therapeutic vaccination is promising, both conceptually and clinically. However, this process is laborious, time-consuming, costly, and hence less likely to solve the global cancer crisis. Therefore, it is proposed to re-focus on personalized anticancer vaccinations to enhance the immunogenicity of autologous therapeutic tumor vaccines. Recent work re-established the idea of using the alarming agents of the immune system, oxidative modifications, as an intrinsic adjuvant to broaden the antitumor T cell receptor repertoire in cancer patients. The key novelty is the use of gas plasma, a multi-reactive oxygen and nitrogen species-generating technology, for diversifying oxidative protein modifications in a, so far, unparalleled manner. This significant innovation has been successfully used in proof-of-concept studies and awaits broader recognition and implementation to explore its chances and limitations of providing affordable personalized anticancer vaccines in the future. Such multidisciplinary advance is timely, as the current COVID-19 crisis is inexorably reflecting the utmost importance of innovative and effective vaccinations in modern times. Full article

(This article belongs to the Special Issue Advances in Vaccine Development)

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