Special Issue "Research in Immune Responses to Vaccines Antigen during Influenza A Infection"

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

Deadline for manuscript submissions: closed (31 August 2021).

Special Issue Editors

Dr. Yoichi Furuya
E-Mail Website
Guest Editor
Department of Immunology & Microbial Disease, Albany Medical College, 47 New Scotland Avenue, MC-151, Albany, NY 12208-3479, USA
Interests: influenza virus; host-pathogen interaction; vaccines; immunology; asthma
Dr. Danushka Wijesundara
E-Mail Website
Guest Editor
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia
Interests: vaccines; immunology; epidemics; virology; indigenous health

Special Issue Information

Dear Colleagues,

Current vaccination strategies against influenza are clearly inadequate, primarily due to the ever-changing nature of the influenza viruses. Thus, a significant clinical need exists for better influenza vaccines that can provide broader and long-lasting protection not only in healthy individuals but also in highly susceptible groups such as the elderly. This Special Issue of Vaccines will cover all aspects of influenza vaccines in the hope that new ideas and latest results will aid development of better vaccination strategies against influenza infections.

Dr. Yoichi Furuya
Dr. Danushka Wijesundara
Guest Editors

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 papers will be 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 2000 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
  • Vaccine
  • Immunity
  • Universal influenza vaccine

Published Papers (9 papers)

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Editorial

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Editorial
Fear of Influenza Resurgence amid COVID-19 Pandemic: Need for Effective Flu Vaccine Still Exists
Vaccines 2021, 9(10), 1198; https://doi.org/10.3390/vaccines9101198 - 18 Oct 2021
Viewed by 422
Abstract
As influenza season was approaching in 2020, public health officials feared that influenza would worsen the COVID-19 situation [...] Full article

Research

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Article
Elderly Subjects Supplemented with L-Glutamine Shows an Improvement of Mucosal Immunity in the Upper Airways in Response to Influenza Virus Vaccination
Vaccines 2021, 9(2), 107; https://doi.org/10.3390/vaccines9020107 - 31 Jan 2021
Cited by 6 | Viewed by 1122
Abstract
Background: Although glutamine is able to improve the immune response, its action in the upper airway immunity against the influenza virus vaccine remains unclear. Therefore, we aimed to evaluate the L-glutamine supplementation effect on the mucosal immune/inflammatory response of elderly subjects vaccinated against [...] Read more.
Background: Although glutamine is able to improve the immune response, its action in the upper airway immunity against the influenza virus vaccine remains unclear. Therefore, we aimed to evaluate the L-glutamine supplementation effect on the mucosal immune/inflammatory response of elderly subjects vaccinated against the influenza virus. Methods: Saliva sampling from 83 physically active elderly volunteers were collected pre- and 30 days after influenza virus vaccination and supplementation with L-glutamine (Gln, n = 42) or placebo (PL, n = 41). Results: Gln group showed higher salivary levels of interleukin (IL)-17, total secretory immunoglobulin A (SIgA), and specific-SIgA post-vaccination than values found pre-vaccination and in the PL group post-vaccination. Whereas higher salivary levels of IL-6 and IL-10 were observed post-vaccination in the Gln group, IL-37 levels were lower post-vaccination in both groups than the values pre-vaccination. Tumor necrosis factor (TNF)-α levels were unchanged. Positive correlations between IL-6 and IL-10 were found in all volunteer groups pre- and post-vaccination and also between IL-17 and IL-6 or IL-10 in the Gln group post-vaccination. A negative correlation between IL-37 and IL-10 was found pre- and post-vaccination in the PL group. Conclusion: Gln supplementation was able to modulate salivary cytokine profile and increase SIgA levels, both total and specific to the influenza virus vaccine, in physically active elderly subjects. Full article
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Article
Adjuvant Selection for Influenza and RSV Prefusion Subunit Vaccines
Vaccines 2021, 9(2), 71; https://doi.org/10.3390/vaccines9020071 - 20 Jan 2021
Cited by 4 | Viewed by 1096
Abstract
Subunit vaccines exhibit favorable safety and immunogenicity profiles and can be designed to mimic native antigen structures. However, pairing with an appropriate adjuvant is imperative in order to elicit effective humoral and cellular immune responses. In this study, we aimed to determine an [...] Read more.
Subunit vaccines exhibit favorable safety and immunogenicity profiles and can be designed to mimic native antigen structures. However, pairing with an appropriate adjuvant is imperative in order to elicit effective humoral and cellular immune responses. In this study, we aimed to determine an optimal adjuvant pairing with the prefusion form of influenza haemagglutinin (HA) or respiratory syncytial virus (RSV) fusion (F) subunit vaccines in BALB/c mice in order to inform future subunit vaccine adjuvant selection. We tested a panel of adjuvants, including aluminum hydroxide (alhydrogel), QS21, Addavax, Addavax with QS21 (AdQS21), and Army Liposome Formulation 55 with monophosphoryl lipid A and QS21 (ALF55). We found that all adjuvants elicited robust humoral responses in comparison to placebo, with the induction of potent neutralizing antibodies observed in all adjuvanted groups against influenza and in AdQS21, alhydrogel, and ALF55 against RSV. Upon HA vaccination, we observed that none of the adjuvants were able to significantly increase the frequency of CD4+ and CD8+ IFN-γ+ cells when compared to unadjuvanted antigen. The varying responses to antigens with each adjuvant highlights that those adjuvants most suited for pairing purposes can vary depending on the antigen used and/or the desired immune response. We therefore suggest that an adjuvant trial for different subunit vaccines in development would likely be necessary in preclinical studies. Full article
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Article
Influenza Vaccination and Myo-Pericarditis in Patients Receiving Immune Checkpoint Inhibitors: Investigating the Likelihood of Interaction through the Vaccine Adverse Event Reporting System and VigiBase
Vaccines 2021, 9(1), 19; https://doi.org/10.3390/vaccines9010019 - 04 Jan 2021
Cited by 3 | Viewed by 1853
Abstract
Background: Evidence on whether the influenza vaccine could exacerbate immune-related adverse events, including myopericarditis (MP), in patients treated with immune checkpoint inhibitors (ICIs), is still conflicting. We explored this issue through a global real-world approach. Methods: We queried the Vaccine Adverse Event Reporting [...] Read more.
Background: Evidence on whether the influenza vaccine could exacerbate immune-related adverse events, including myopericarditis (MP), in patients treated with immune checkpoint inhibitors (ICIs), is still conflicting. We explored this issue through a global real-world approach. Methods: We queried the Vaccine Adverse Event Reporting System (VAERS) and VigiBase to retrieve cases of MP in which the influenza vaccine and ICIs were recorded as suspect and were concomitantly reported. For the included cases, causality assessment and Drug Interaction Probability Scale (DIPS) algorithms were applied. Results: There were 191 and 399 reports of MP with the influenza vaccine that were retrieved (VAERS and VigiBase, respectively). No case of MP reporting the concomitant use of ICIs and the influenza vaccine was found in VAERS, while three cases of myocarditis were retrieved in VigiBase. All of the cases were unclassifiable for a causality assessment because of the lack of data concerning latency. According to the DIPS, one report was categorized as possible and two as doubtful. Conclusion: The paucity of cases coupled with the doubtful causality assessment make the potential interaction between influenza vaccines and ICIs in cancer patients negligible from clinical and epidemiological standpoints. These findings support the cardiovascular safety of the influenza vaccination, which remains strongly recommended in cancer patients, especially in the current COVID-19 era. Full article
Article
Influenza Vaccination and Non-Pharmaceutical Measure Effectiveness for Preventing Influenza Outbreaks in Schools: A Surveillance-Based Evaluation in Beijing
Vaccines 2020, 8(4), 714; https://doi.org/10.3390/vaccines8040714 - 01 Dec 2020
Cited by 1 | Viewed by 653
Abstract
Although schools are known to play a major role in the spread of influenza virus, few studies have evaluated the effectiveness of vaccination and non-pharmaceutical measures for preventing influenza outbreaks in schools. We investigated all febrile illness outbreaks in primary and secondary schools [...] Read more.
Although schools are known to play a major role in the spread of influenza virus, few studies have evaluated the effectiveness of vaccination and non-pharmaceutical measures for preventing influenza outbreaks in schools. We investigated all febrile illness outbreaks in primary and secondary schools in Beijing reported between August 2018 and July 2019. We obtained epidemiological information on febrile illness outbreaks and oral pharyngeal swabs from students in the outbreaks to test for influenza virus. We surveyed schools that did not report febrile illness outbreaks. We developed multi-level models to identify and evaluate factors associated with serious influenza outbreaks and explored the association of vaccine coverage and outbreaks using multi-stage regression models. We identified a total of 748 febrile illness outbreaks involving 8176 students in Beijing; 462 outbreaks were caused by influenza virus. Adjusted regression modeling showed that large class size (odds ratio (OR) = 2.38) and the number of days from identification of the first case to initiation of an intervention (OR = 1.17) were statistically significant and positively associated with serious outbreaks, and that high vaccination coverage (relative risk (RR) = 0.50) was statistically significant and negatively associated with outbreaks. Multi-stage regression modeling showed that RR decreased fastest when vaccination coverage was 45% to 51%. We conclude that high influenza vaccination coverage can prevent influenza outbreaks in schools and that rapid identification of febrile children and early initiation of non-pharmaceutical measures can reduce outbreak size. Full article
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Communication
Impact of Pre-Existing Immunity on Live Attenuated Influenza Vaccine-Induced Cross-Protective Immunity
Vaccines 2020, 8(3), 459; https://doi.org/10.3390/vaccines8030459 - 20 Aug 2020
Cited by 4 | Viewed by 1094
Abstract
The efficacy of the intranasally (i.n.) delivered live attenuated influenza vaccine (LAIV) is variable and, in some seasons, suboptimal. In this study, we report that LAIV exhibits cross-protective efficacy in mice, potentially associated with cellular immunity as opposed to antigen-specific antibody responses. However, [...] Read more.
The efficacy of the intranasally (i.n.) delivered live attenuated influenza vaccine (LAIV) is variable and, in some seasons, suboptimal. In this study, we report that LAIV exhibits cross-protective efficacy in mice, potentially associated with cellular immunity as opposed to antigen-specific antibody responses. However, pre-exposure to the intramuscularly (i.m.) delivered inactivated influenza vaccine (IIV) severely impaired LAIV-induced cross-protection against heterologous challenge, potentially by inhibiting replication of LAIV. Our findings suggest that pre-existing immunity afforded by IIV suppresses cross-protective T cell immunogenicity of LAIV. Full article
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Review

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Review
Antibody Focusing to Conserved Sites of Vulnerability: The Immunological Pathways for ‘Universal’ Influenza Vaccines
Vaccines 2021, 9(2), 125; https://doi.org/10.3390/vaccines9020125 - 05 Feb 2021
Cited by 4 | Viewed by 922
Abstract
Influenza virus remains a serious public health burden due to ongoing viral evolution. Vaccination remains the best measure of prophylaxis, yet current seasonal vaccines elicit strain-specific neutralizing responses that favor the hypervariable epitopes on the virus. This necessitates yearly reformulations of seasonal vaccines, [...] Read more.
Influenza virus remains a serious public health burden due to ongoing viral evolution. Vaccination remains the best measure of prophylaxis, yet current seasonal vaccines elicit strain-specific neutralizing responses that favor the hypervariable epitopes on the virus. This necessitates yearly reformulations of seasonal vaccines, which can be limited in efficacy and also shortchange pandemic preparedness. Universal vaccine development aims to overcome these deficits by redirecting antibody responses to functionally conserved sites of viral vulnerability to enable broad coverage. However, this is challenging as such antibodies are largely immunologically silent, both following vaccination and infection. Defining and then overcoming the immunological basis for such subdominant or ‘immuno-recessive’ antibody targeting has thus become an important aspect of universal vaccine development. This, coupled with structure-guided immunogen design, has led to proof-of-concept that it is possible to rationally refocus humoral immunity upon normally ‘unseen’ broadly neutralizing antibody targets on influenza virus. Full article
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Review
The Next Generation of Influenza Vaccines: Towards a Universal Solution
Vaccines 2021, 9(1), 26; https://doi.org/10.3390/vaccines9010026 - 07 Jan 2021
Cited by 6 | Viewed by 2503
Abstract
Influenza viruses remain a constant burden in humans, causing millions of infections and hundreds of thousands of deaths each year. Current influenza virus vaccine modalities primarily induce antibodies directed towards the highly variable head domain of the hemagglutinin protein on the virus surface. [...] Read more.
Influenza viruses remain a constant burden in humans, causing millions of infections and hundreds of thousands of deaths each year. Current influenza virus vaccine modalities primarily induce antibodies directed towards the highly variable head domain of the hemagglutinin protein on the virus surface. Such antibodies are often strain-specific, meaning limited cross-protection against divergent influenza viruses is induced, resulting in poor vaccine efficacy. To attempt to counteract this, yearly influenza vaccination with updated formulations containing antigens from more recently circulating viruses is required. This is an expensive and time-consuming exercise, and the constant arms race between host immunity and virus evolution presents an ongoing challenge for effective vaccine development. Furthermore, there exists the constant pandemic threat of highly pathogenic avian influenza viruses with high fatality rates (~30–50%) or the emergence of new, pathogenic reassortants. Current vaccines would likely offer little to no protection from such viruses in the event of an epidemic or pandemic. This highlights the urgent need for improved influenza virus vaccines capable of providing long-lasting, robust protection from both seasonal influenza virus infections as well as potential pandemic threats. In this narrative review, we examine the next generation of influenza virus vaccines for human use and the steps being taken to achieve universal protection. Full article
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Other

Commentary
Impact of Pre-Existing Immunity to Influenza on Live-Attenuated Influenza Vaccine (LAIV) Immunogenicity
Vaccines 2020, 8(4), 683; https://doi.org/10.3390/vaccines8040683 - 16 Nov 2020
Cited by 2 | Viewed by 804
Abstract
During the previous influenza seasons, between 2010 and 2016, the live attenuated influenza vaccine (LAIV) provided variable efficacy against influenza in the U.S., causing the recommendation against the use of the LAIV. In striking contrast, pre-clinical studies have repeatedly demonstrated superior efficacy of [...] Read more.
During the previous influenza seasons, between 2010 and 2016, the live attenuated influenza vaccine (LAIV) provided variable efficacy against influenza in the U.S., causing the recommendation against the use of the LAIV. In striking contrast, pre-clinical studies have repeatedly demonstrated superior efficacy of LAIV against mismatched influenza viruses, compared to inactivated influenza vaccines (IIV). This disparity in reported vaccine efficacies between pre-clinical and clinical studies may in part be explained by limitations of the animal models of influenza. In particular, the absence of pre-existing immunity in animal models has recently emerged as a potential explanation for the discrepancies between preclinical findings and human studies. This commentary focuses on the potential impact of pre-existing immunity on LAIV induced immunogenicity with an emphasis on cross-protective immunity. Full article
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