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Vaccines
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The Recent Development of Influenza Vaccine
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The Recent Development of Influenza Vaccine

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Influenza Virus Vaccines".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 16145

Special Issue Editor

Dr. Ramireddy Bommireddy

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
Interests: influenza; older population; adjuvants; universal vaccine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the increased importance of influenza vaccination in the elderly due to increased morbidity and mortality, vaccine efficacy is only 17–53% versus 70–90% in young adults. The development of vaccines for an ever-increasing aging population has been an arduous challenge due to immunosenescence. Some of the approaches to improve vaccine efficacy in the elderly include high-dose vaccines and use of better adjuvants. Currently, a high-dose influenza vaccine and adjuvanted vaccines have been approved in the US for the elderly, 65 years and older. These influenza vaccines induce elevated hemagglutination inhibition (HAI) titers by enhancing the immunogenicity of vaccines. The efficacy of controlling lung viral replication by vaccination with adjuvants that induce antibodies, CD4 and CD8 T cell responses is desirable. Recent advances in developing universal vaccines that generate immunity against stalk proteins might provide better protection against various strains of influenza virus. We welcome articles that provide the latest developments in the vaccine and novel adjuvants and mechanisms of long-term efficacy studies or review articles in this area for this Special Issue.

Dr. Ramireddy Bommireddy
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • influenza
  • older population
  • adjuvants
  • universal vaccine

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Published Papers (7 papers)

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Research

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26 pages, 1536 KiB  
Article
A Broad Influenza Vaccine Based on a Heat-Activated, Tissue-Restricted Replication-Competent Herpesvirus
by Nuria Vilaboa, David C. Bloom, William Canty and Richard Voellmy
Vaccines 2024, 12(7), 703; https://doi.org/10.3390/vaccines12070703 - 23 Jun 2024
Viewed by 1096
Abstract
Vaccination with transiently activated replication-competent controlled herpesviruses (RCCVs) expressing influenza A virus hemagglutinins broadly protects mice against lethal influenza virus challenges. The non-replicating RCCVs can be activated to transiently replicate with high efficiency. Activation involves a brief heat treatment to the epidermal administration [...] Read more.
Vaccination with transiently activated replication-competent controlled herpesviruses (RCCVs) expressing influenza A virus hemagglutinins broadly protects mice against lethal influenza virus challenges. The non-replicating RCCVs can be activated to transiently replicate with high efficiency. Activation involves a brief heat treatment to the epidermal administration site in the presence of a drug. The drug co-control is intended as a block to inadvertent reactivation in the nervous system and, secondarily, viremia under adverse conditions. While the broad protective effects observed raise an expectation that RCCVs may be developed as universal flu vaccines, the need for administering a co-activating drug may dampen enthusiasm for such a development. To replace the drug co-control, we isolated keratin gene promoters that were active in skin cells but inactive in nerve cells and other cells in vitro. In a mouse model of lethal central nervous system (CNS) infection, the administration of a recombinant that had the promoter of the infected cell protein 8 (ICP8) gene of a wild-type herpes simplex virus 1 (HSV-1) strain replaced by a keratin promoter did not result in any clinical signs, even at doses of 500 times wild-type virus LD50. Replication of the recombinant was undetectable in brain homogenates. Second-generation RCCVs expressing a subtype H1 hemagglutinin (HA) were generated in which the infected cell protein 4 (ICP4) genes were controlled by a heat switch and the ICP8 gene by the keratin promoter. In mice, these RCCVs replicated efficiently and in a heat-controlled fashion in the epidermal administration site. Immunization with the activated RCCVs induced robust neutralizing antibody responses against influenza viruses and protected against heterologous and cross-group influenza virus challenges. Full article
(This article belongs to the Special Issue The Recent Development of Influenza Vaccine)
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25 pages, 1876 KiB  
Article
Very Broadly Effective Hemagglutinin-Directed Influenza Vaccines with Anti-Herpetic Activity
by David C. Bloom, Cameron Lilly, William Canty, Nuria Vilaboa and Richard Voellmy
Vaccines 2024, 12(5), 537; https://doi.org/10.3390/vaccines12050537 - 14 May 2024
Cited by 1 | Viewed by 1469
Abstract
A universal vaccine that generally prevents influenza virus infection and/or illness remains elusive. We have been exploring a novel approach to vaccination involving replication-competent controlled herpesviruses (RCCVs) that can be deliberately activated to replicate efficiently but only transiently in an administration site in [...] Read more.
A universal vaccine that generally prevents influenza virus infection and/or illness remains elusive. We have been exploring a novel approach to vaccination involving replication-competent controlled herpesviruses (RCCVs) that can be deliberately activated to replicate efficiently but only transiently in an administration site in the skin of a subject. The RCCVs are derived from a virulent wild-type herpesvirus strain that has been engineered to contain a heat shock promoter-based gene switch that controls the expression of, typically, two replication-essential viral genes. Additional safety against inadvertent replication is provided by an appropriate secondary mechanism. Our first-generation RCCVs can be activated at the administration site by a mild local heat treatment in the presence of an antiprogestin. Here, we report that epidermal vaccination with such RCCVs expressing a hemagglutinin or neuraminidase of an H1N1 influenza virus strain protected mice against lethal challenges by H1N1 virus strains representing 75 years of evolution. Moreover, immunization with an RCCV expressing a subtype H1 hemagglutinin afforded full protection against a lethal challenge by an H3N2 influenza strain, and an RCCV expressing a subtype H3 hemagglutinin protected against a lethal challenge by an H1N1 strain. Vaccinated animals continued to gain weight normally after the challenge. Protective effects were even observed in a lethal influenza B virus challenge. The RCCV-based vaccines induced robust titers of in-group, cross-group and even cross-type neutralizing antibodies. Passive immunization suggested that observed vaccine effects were at least partially antibody-mediated. In summary, RCCVs expressing a hemagglutinin induce robust and very broad cross-protective immunity against influenza. Full article
(This article belongs to the Special Issue The Recent Development of Influenza Vaccine)
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15 pages, 1599 KiB  
Article
Effects of Influenza Vaccine on the Immune Responses to SARS-CoV-2 Vaccination
by A. Riccomi, C. M. Trombetta, M. Dorrucci, D. Di Placido, N. Sanarico, F. Farchi, R. Giuseppetti, U. Villano, C. Marcantonio, S. Marchi, A. Ciaramella, P. Pezzotti, E. Montomoli, C. Valdarchi, A. R. Ciccaglione and S. Vendetti
Vaccines 2024, 12(4), 425; https://doi.org/10.3390/vaccines12040425 - 17 Apr 2024
Viewed by 1681
Abstract
A number of studies have suggested that influenza vaccination can provide protection against COVID-19, but the underlying mechanisms that could explain this association are still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the [...] Read more.
A number of studies have suggested that influenza vaccination can provide protection against COVID-19, but the underlying mechanisms that could explain this association are still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. A total of 113 participants were enrolled, 74 of whom had no prior COVID-19 diagnosis or significant comorbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARS-CoV-2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARS-CoV-2 vaccinations compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to the influenza vaccine was evaluated, and individuals were stratified as high or low responders. High responders showed increased antibody titers against the SARS-CoV-2 vaccine both after 4 and 12 weeks post-vaccination. Conversely, individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host’s intrinsic ability to respond to stimuli play a role in the response to the vaccine. Full article
(This article belongs to the Special Issue The Recent Development of Influenza Vaccine)
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10 pages, 250 KiB  
Article
Poverty and Influenza/Pneumococcus Vaccinations in Older People: Data from The Survey of Health, Ageing and Retirement in Europe (SHARE) Study
by Nicola Veronese, Nancy Zambon, Marianna Noale and Stefania Maggi
Vaccines 2023, 11(9), 1422; https://doi.org/10.3390/vaccines11091422 - 27 Aug 2023
Cited by 1 | Viewed by 1937
Abstract
Vaccine acceptance seems to be lower in poor people. The determinants of the lower vaccine coverage in poor people are not established. Therefore, we aimed to explore the association between poverty and influenza/pneumococcus vaccinations and the factors potentially associated with vaccination’s coverage in [...] Read more.
Vaccine acceptance seems to be lower in poor people. The determinants of the lower vaccine coverage in poor people are not established. Therefore, we aimed to explore the association between poverty and influenza/pneumococcus vaccinations and the factors potentially associated with vaccination’s coverage in poor people. The data of the Survey of Health, Ageing and Retirement in Europe (SHARE), an ongoing longitudinal, multi-disciplinary, and cross-national European study where used. Poverty was defined using information on income and household size. Among 47,370 participants initially included in the SHARE study, 12,442 were considered poor. In the multivariable logistic regression analysis, “Household size” was associated with a significantly lower vaccination probability, meanwhile “Age”, “Years of education”, “Regularly taking prescription drugs”, and the level of income were significantly associated with higher probabilities of both influenza and pneumonia vaccinations. The “Number of illnesses/health conditions” was significantly associated with a higher probability of getting vaccination against influenza and against pneumococcus. In conclusion, among poor older people, several specific factors could be identified as barriers for the vaccinations against influenza or pneumococcus that are unique to this segment of the population, such as living with the family and having a job. Full article
(This article belongs to the Special Issue The Recent Development of Influenza Vaccine)
18 pages, 4473 KiB  
Article
Truncation of NS1 Protein Enhances T Cell-Mediated Cross-Protection of a Live Attenuated Influenza Vaccine Virus Expressing Wild-Type Nucleoprotein
by Polina Prokopenko, Victoria Matyushenko, Alexandra Rak, Ekaterina Stepanova, Anna Chistyakova, Arina Goshina, Igor Kudryavtsev, Larisa Rudenko and Irina Isakova-Sivak
Vaccines 2023, 11(3), 501; https://doi.org/10.3390/vaccines11030501 - 21 Feb 2023
Cited by 5 | Viewed by 2628
Abstract
Current seasonal influenza vaccines have suboptimal effectiveness, especially in seasons dominated by viruses that do not match the vaccine. Therefore, finding new approaches to improve the immunogenicity and efficacy of traditional influenza vaccines is of high priority for public health. Licensed live attenuated [...] Read more.
Current seasonal influenza vaccines have suboptimal effectiveness, especially in seasons dominated by viruses that do not match the vaccine. Therefore, finding new approaches to improve the immunogenicity and efficacy of traditional influenza vaccines is of high priority for public health. Licensed live attenuated influenza vaccine (LAIV) is a promising platform for designing broadly protective vaccines due to its ability to induce cross-reactive T-cell immunity. In this study, we tested the hypothesis that truncation of the nonstructural protein 1 (NS1) and the replacement of the nucleoprotein (NP) of the A/Leningrad/17 master donor virus with a recent NP, i.e., switching to 5:3 genome composition, could improve the cross-protective potential of the LAIV virus. We generated a panel of LAIV candidates differing from the classical vaccine by the source of NP gene and/or by the length of NS1 protein. We showed that NS1-modified LAIV viruses had reduced viral replication in the respiratory tract of mice, indicating a more attenuated phenotype compared to the LAIVs with full-length NS1. Most importantly, the LAIV candidate with both NP and NS genes modified induced a robust systemic and lung-localized memory CD8 T-cell response targeting more recent viruses, and better protected immunized mice against lethal challenge with a heterosubtypic influenza virus than the control LAIV variant. Overall, these data indicate that the 5:3 LAIVs with truncated NS1 may be beneficial for protection against heterologous influenza viruses and warrant further preclinical and clinical development. Full article
(This article belongs to the Special Issue The Recent Development of Influenza Vaccine)
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17 pages, 7499 KiB  
Article
Expression of Influenza M2e-NP Recombinant Fusion Protein in Escherichia coli BL21 (DE3) and Its Binding to Antibodies
by Mei Peng Tan, Noorjahan Banu Mohamed Alitheen, Wen Siang Tan and Wei Boon Yap
Vaccines 2022, 10(12), 2066; https://doi.org/10.3390/vaccines10122066 - 1 Dec 2022
Cited by 2 | Viewed by 2419
Abstract
The current influenza vaccines only confer protection against the circulating influenza subtypes, therefore universal vaccines are needed to prevent upcoming influenza outbreaks caused by emerging influenza subtypes. The extracellular domain of influenza A M2 protein (M2e) is highly conserved among different subtypes of [...] Read more.
The current influenza vaccines only confer protection against the circulating influenza subtypes, therefore universal vaccines are needed to prevent upcoming influenza outbreaks caused by emerging influenza subtypes. The extracellular domain of influenza A M2 protein (M2e) is highly conserved among different subtypes of influenza A viruses, and it is able to elicit protective immunity against the viruses. The influenza nucleoprotein (NP) was used to display the M2e in this study due to its promising T-cell response and adjuvanticity. The M2e gene was fused to the 5′-end of the NP gene and then cloned into pRSET B vector. The DNA sequencing analysis revealed six point mutations in the M2e-NP fusion gene, including one mutation in the M2e peptide and five mutations in the NP. The mutations were reverted using PCR site-directed mutagenesis. The recombinant plasmids (pRSET B-M2e-NP and pRSET B-mM2e-NP) were introduced into Escherichia coli (E. coli) BL21 (DE3) for protein expression. The mutated and non-mutated proteins were subsequently expressed and named mM2e-NP and M2e-NP, respectively. The expression of mM2e-NP and M2e-NP was not affected by the mutations. The binding of anti-M2e antibody to the purified native mM2e-NP and M2e-NP also remained active. However, when the anti-NP antibody was tested, the signal produced by mM2e-NP was very weak. The results implied that the amino acid changes in the NP had adversely impacted on the conformation of mM2e-NP and subsequently affected the antibody binding. In light of the remarkable antibody binding to the M2e-NP fusion protein, this study highly recommends the potential of M2e-NP as a universal influenza vaccine candidate. Full article
(This article belongs to the Special Issue The Recent Development of Influenza Vaccine)
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Review

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12 pages, 1221 KiB  
Review
Cap-Independent Circular mRNA Translation Efficiency
by Andrei A. Deviatkin, Ruslan A. Simonov, Kseniya A. Trutneva, Anna A. Maznina, Anastasiia B. Soroka, Anna A. Kogan, Sofya G. Feoktistova, Elena M. Khavina, Olga N. Mityaeva and Pavel Y. Volchkov
Vaccines 2023, 11(2), 238; https://doi.org/10.3390/vaccines11020238 - 20 Jan 2023
Cited by 7 | Viewed by 3998
Abstract
Recently, the mRNA platform has become the method of choice in vaccine development to find new ways to fight infectious diseases. However, this approach has shortcomings, namely that mRNA vaccines require special storage conditions, which makes them less accessible. This instability is due [...] Read more.
Recently, the mRNA platform has become the method of choice in vaccine development to find new ways to fight infectious diseases. However, this approach has shortcomings, namely that mRNA vaccines require special storage conditions, which makes them less accessible. This instability is due to the fact that the five-prime and three-prime ends of the mRNA are a substrate for the ubiquitous exoribonucleases. To address the problem, circular mRNAs have been proposed for transgene delivery as they lack these ends. Notably, circular RNAs do not have a capped five-prime end, which makes it impossible to initiate translation canonically. In this review, we summarize the current knowledge on cap-independent translation initiation methods and discuss which approaches might be most effective in developing vaccines and other biotechnological products based on circular mRNAs. Full article
(This article belongs to the Special Issue The Recent Development of Influenza Vaccine)
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