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Vaccines
Special Issues
Immunity to Influenza Viruses and Vaccines
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Immunity to Influenza Viruses and Vaccines

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

Deadline for manuscript submissions: 31 January 2026 | Viewed by 7125

Special Issue Editor

Dr. Rongbao Gao

E-Mail Website
Guest Editor
Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Interests: etiology, immunology and vaccinology of influenza viruses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Influenza viruses are highly prevalent pathogens transmitted by air droplets or direct contact. Vaccination is the recommended strategy for the prevention and control of influenza. Both previous influenza infections and vaccinations shape individual immunity and impact vaccine response. Immunity to influenza comprises both innate and adaptive components. To promote the development of control and prevention of influenza, we are launching a Special Issue entitled “Immunity to Influenza Viruses and Vaccines”. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: antiviral and anti-influenza immunity, immunological responses to potential viral vaccine antigens, the delivery methods of viral vaccine antigens, studies on vaccine adjuvants related to viral vaccine development, investigations of viral vaccine strategies that aim to raise broadly neutralizing antibodies, and theoretical studies that suggest and rationalize novel types of viral vaccines or novel ways of stimulating protective antiviral immunity. We look forward to receiving your contributions.

Dr. Rongbao Gao
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

  • avian influenza
  • etiology
  • antiviral immunity
  • serology
  • vaccine
  • pathogenesis

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Published Papers (5 papers)

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Research

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13 pages, 1064 KiB  
Article
Prevention of Cardiovascular Diseases with Standard-Dose Quadrivalent Influenza Vaccine in People Aged ≥50 Years in Australia During the 2017 A/H3N2 Epidemic
by Zubair Akhtar, Aye M. Moa, Timothy C. Tan, Ole Fröbert, Robert Menzies and C. Raina MacIntyre
Vaccines 2025, 13(4), 407; https://doi.org/10.3390/vaccines13040407 - 14 Apr 2025
Viewed by 701
Abstract
Background: In Australia, 2017 was a severe A/H3N2 season and, therefore, we estimated the effectiveness of standard-dose quadrivalent influenza vaccine in preventing hospitalization for cardiovascular disease (CVD) among New South Wales (NSW) residents aged ≥50 years. Methods: We conducted a nested, matched case–control [...] Read more.
Background: In Australia, 2017 was a severe A/H3N2 season and, therefore, we estimated the effectiveness of standard-dose quadrivalent influenza vaccine in preventing hospitalization for cardiovascular disease (CVD) among New South Wales (NSW) residents aged ≥50 years. Methods: We conducted a nested, matched case–control study within the 45 and Up study, linking data from the Australian Immunization Register, NSW Admitted Patient Data Collection and Pharmaceutical Benefits Schedule. Cases were individuals hospitalized for CVD and controls were those who were hospitalized for gastrointestinal diseases. The two groups were balanced using 1:1 propensity score matching based on age group (50–64, 65–74, 75–84, and ≥85 years) and sex. After adjusting for confounders (smoking, body mass index and income), we calculated the adjusted odds ratio (aOR) for vaccination during the season using multivariable logistic regression. E-values were estimated to assess residual confounding. Vaccine effectiveness (VE) was calculated as (1 − aOR) × 100. Results: There were 10,445 (4452 cases and 5993 controls) study participants. After matching, 8904 (85.2%) were retained with a mean age of 76.4 ± 10.4 years and 58.3% men. Following adjustment for confounders, the aOR of averting a CVD hospitalization was 0.15 (95% CI: 0.13 to 0.17; p < 0.001). The estimated VE against CVD hospitalization was 85% (95% CI: 83 to 87). We found an E-value of 12.82, indicating strong evidence of minimal residual confounding. Conclusions: In the severe 2017 influenza A/H3N2 season in Australia, we observed a high VE in preventing cardiovascular hospitalization despite a low VE against influenza infection prevention. Improving vaccine uptake may reduce cardiovascular burden. Full article
(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)
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17 pages, 1940 KiB  
Article
Application of Humanized MHC Transgenic Mice in the Screening of HLA–Restricted T Cell Epitopes for Influenza Vaccines
by Yuwei Wei, Keyu Sun, Xuelian Han, Yali Sun, Jiejie Zhang, Yuan Wang, Qi Yin, Tiantian Yang, Kai Yuan, Min Li and Guangyu Zhao
Vaccines 2025, 13(3), 331; https://doi.org/10.3390/vaccines13030331 - 20 Mar 2025
Viewed by 455
Abstract
Background: Annual influenza epidemics pose a significant burden on the global healthcare system. The currently available vaccines mainly induce the production of neutralizing antibodies against hemagglutinin and neuraminidase, which are prone to antigenic variation, and this can reduce vaccine efficacy. Vaccines designed to [...] Read more.
Background: Annual influenza epidemics pose a significant burden on the global healthcare system. The currently available vaccines mainly induce the production of neutralizing antibodies against hemagglutinin and neuraminidase, which are prone to antigenic variation, and this can reduce vaccine efficacy. Vaccines designed to target T cell epitopes can be potentially valuable. Considering the difficulties in obtaining clinical samples and the unique advantages of mice in disease-related research, a mouse model that can simulate human immune responses can be a superior alternative to peripheral blood mononuclear cells for epitope screening. Methods: The T cell epitopes of the A/California/07/2009 (H1N1) virus were predicted and utilized to evaluate the cellular immune responses of HLA-A2/DR1 and HLA-A11/DR1 transgenic mice during epitope screening. The selected peptides were used to immunize these two groups of transgenic mice, followed by a viral challenge to assess their protective efficacy. Results: The epitopes that were predicted and screened could stimulate cellular immune responses in HLA-A2/DR1 transgenic mice, HLA-A11/DR1 transgenic mice, and C57BL/6 mice. Moreover, the transgenic mice exhibited stronger ability to produce IFN-γ than that of the wild-type mice. Upon immunization and subjecting to viral challenge, the selected peptides exhibited protective effects against the influenza virus. Conclusions: The HLA-A2/DR1 and HLA-A11/DR1 transgenic mouse models can be used for the direct screening and validation of influenza virus T cell epitopes, which is crucial for designing T cell epitope vaccines against influenza viruses. Further, this method can be applied in epitope screening and vaccine designing before the spread of other emerging and sudden infectious diseases, thereby supporting epidemic control. Full article
(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)
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20 pages, 3598 KiB  
Article
Cross-Reactive Fc-Mediated Antibody Responses to Influenza HA Stem Region in Human Sera Following Seasonal Vaccination
by Ayae Nishiyama, Takuto Nogimori, Yuji Masuta, Tomoka Matsuura, Tetsuo Kase, Kyoko Kondo, Satoko Ohfuji, Yu Nakagama, Natsuko Kaku, Sachie Nakagama, Yuko Nitahara, Yoshimasa Takahashi, Hiroshi Kakeya, Yasutoshi Kido, Wakaba Fukushima and Takuya Yamamoto
Vaccines 2025, 13(2), 140; https://doi.org/10.3390/vaccines13020140 - 28 Jan 2025
Viewed by 1155
Abstract
Background: Current influenza A vaccines primarily induce neutralizing antibodies targeting the variable hemagglutinin (HA) head domain, limiting their effectiveness against diverse or emerging influenza A virus (IAV) subtypes. The conserved HA stem domain, particularly the long α-helix (LAH) epitope, is a focus of [...] Read more.
Background: Current influenza A vaccines primarily induce neutralizing antibodies targeting the variable hemagglutinin (HA) head domain, limiting their effectiveness against diverse or emerging influenza A virus (IAV) subtypes. The conserved HA stem domain, particularly the long α-helix (LAH) epitope, is a focus of universal vaccine research due to its cross-protective potential. Additionally, Fc-mediated functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are recognized as important protective immune mechanisms. This study evaluated IgG responses to the HA head, stem, and LAH regions and assessed cross-reactive potential through neutralization, ADCC, and ADCP assays. Methods: IgG responses to the HA head, stem, and LAH regions were measured in vaccinated individuals. Functional assays were conducted for neutralization, ADCC, and ADCP to evaluate the association between antibody levels and immune function. Results: The results showed that HA head-specific IgG increased significantly after vaccination in 50 individuals, whereas stem-specific IgG increased by 72% and LAH-specific IgG by 12–14%. Among the induced antibody subclasses, IgG1 was predominantly increased. Neutralization titers were detected in viruses of the same strain as the vaccine strain, but not in classical or pandemic strains (H5N1, H7N9). HA stem-specific IgG1 antibody titers showed a significant correlation with ADCC/ADCP activity breadth, but no correlation was observed with neutralization breadth. Conclusions: These findings suggest that although current influenza vaccines can induce HA stem-targeted cross-reactive antibodies, their quantity may be insufficient for broad cross-protection, underscoring the need for improved vaccine strategies. Full article
(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)
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23 pages, 6419 KiB  
Article
Adjuvant Use of the Invariant-Natural-Killer-T-Cell Agonist α-Galactosylceramide Leads to Vaccine-Associated Enhanced Respiratory Disease in Influenza-Vaccinated Pigs
by Bianca L. Artiaga, Daniel Madden, Taeyong Kwon, Chester McDowell, Cassidy Keating, Velmurugan Balaraman, Darling Melany de Carvahlo Madrid, Laurie Touchard, Jamie Henningson, Philip Meade, Florian Krammer, Igor Morozov, Juergen A. Richt and John P. Driver
Vaccines 2024, 12(9), 1068; https://doi.org/10.3390/vaccines12091068 - 18 Sep 2024
Viewed by 1666
Abstract
Invariant natural killer T (iNKT) cells are glycolipid-reactive T cells with potent immunoregulatory properties. iNKT cells activated with the marine-sponge-derived glycolipid, α-galactosylceramide (αGC), provide a universal source of T-cell help that has shown considerable promise for a wide array of therapeutic applications. This [...] Read more.
Invariant natural killer T (iNKT) cells are glycolipid-reactive T cells with potent immunoregulatory properties. iNKT cells activated with the marine-sponge-derived glycolipid, α-galactosylceramide (αGC), provide a universal source of T-cell help that has shown considerable promise for a wide array of therapeutic applications. This includes harnessing iNKT-cell-mediated immune responses to adjuvant whole inactivated influenza virus (WIV) vaccines. An important concern with WIV vaccines is that under certain circumstances, they are capable of triggering vaccine-associated enhanced respiratory disease (VAERD). This immunopathological phenomenon can arise after immunization with an oil-in-water (OIW) adjuvanted WIV vaccine, followed by infection with a hemagglutinin and neuraminidase mismatched challenge virus. This elicits antibodies (Abs) that bind immunodominant epitopes in the HA2 region of the heterologous virus, which purportedly causes enhanced virus fusion activity to the host cell and increased infection. Here, we show that αGC can induce severe VAERD in pigs. However, instead of stimulating high concentrations of HA2 Abs, αGC elicits high concentrations of interferon (IFN)-γ-secreting cells both in the lungs and systemically. Additionally, we found that VAERD mediated by iNKT cells results in distinct cytokine profiles and altered adaptation of the challenge virus following infection compared to an OIW adjuvant. Overall, these results provide a cautionary note about considering the formulation of WIV vaccines with iNKT-cell agonists as a potential strategy to modulate antigen-specific immunity. Full article
(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)
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Review

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19 pages, 587 KiB  
Review
Recent Occurrence, Diversity, and Candidate Vaccine Virus Selection for Pandemic H5N1: Alert Is in the Air
by Yordanka Medina-Armenteros, Daniela Cajado-Carvalho, Ricardo das Neves Oliveira, Milena Apetito Akamatsu and Paulo Lee Ho
Vaccines 2024, 12(9), 1044; https://doi.org/10.3390/vaccines12091044 - 12 Sep 2024
Cited by 1 | Viewed by 2391
Abstract
The prevalence of the highly pathogenic avian influenza virus H5N1 in wild birds that migrate all over the world has resulted in the dissemination of this virus across Asia, Europe, Africa, North and South America, the Arctic continent, and Antarctica. So far, H5N1 [...] Read more.
The prevalence of the highly pathogenic avian influenza virus H5N1 in wild birds that migrate all over the world has resulted in the dissemination of this virus across Asia, Europe, Africa, North and South America, the Arctic continent, and Antarctica. So far, H5N1 clade 2.3.4.4.b has reached an almost global distribution, with the exception of Australia and New Zealand for autochthonous cases. H5N1 clade 2.3.4.4.b, derived from the broad-host-range A/Goose/Guangdong/1/96 (H5N1) lineage, has evolved, adapted, and spread to species other than birds, with potential mammal-to-mammal transmission. Many public health agencies consider H5N1 influenza a real pandemic threat. In this sense, we analyzed H5N1 hemagglutinin sequences from recent outbreaks in animals, clinical samples, antigenic prototypes of candidate vaccine viruses, and licensed human vaccines for H5N1 with the aim of shedding light on the development of an H5N1 vaccine suitable for a pandemic response, should one occur in the near future. Full article
(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines)
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