Special Issue "The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view"

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (28 February 2018)

Special Issue Editor

Guest Editor
Dr. Florian Krammer

Icahn School of Medicine at Mount Sinai, New York, One Gustave L. Levy Place, 10029 NY, Box 1124, USA
Website | E-Mail
Interests: influenza virus; avian influenza; universal influenza virus vaccines; hemagglutinin; neuraminidase; stalk-reactive antibodies; zoonotic viral infections; emerging viruses; viral glycoproteins

Special Issue Information

Dear Colleagues,

Current influenza virus vaccines have many shortfalls. Next-generation vaccines that offer longer lasting, broader and perhaps universal protection against influenza A and B viruses are urgently needed. Recent efforts aim at creating better vaccines that meet these criteria and several candidates are under development. However, there are still severe gaps in our understanding of (vaccine induced) immunity against influenza viruses and filling these gaps is critical on the path forward to better vaccines.

This special issue of Vaccines will give the next generation of influenza virologists (less than 10 years into their first tenure-track appointment) the opportunity to present their view on current gaps, new developments and the future of influenza virus vaccines and vaccine development. Importantly, this special issue aims to gather a wide range of perspectives on influenza virus vaccines ranging from specialists in influenza virus immunology, vaccinology, virus engineering, structural biology, host-pathogen interactions, transmission, surveillance and virus evolution to epidemiology and others.

Dr. Florian Krammer, PhD
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 quarterly 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 650 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
  • influenza virus vaccines
  • heterosubtypic immunity
  • vaccine design
  • antigen design
  • influenza virus immunity

Published Papers (16 papers)

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Editorial

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Open AccessEditorial What’s Fair Is Fair: Leveling the Playing Field for Young Scientists
Received: 29 May 2018 / Accepted: 29 May 2018 / Published: 31 May 2018
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Abstract
Like every MD Ph.D. pup, I was faced with the BIG decision: medicine or science?[...] Full article

Review

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Open AccessReview The Future of Influenza Vaccines: A Historical and Clinical Perspective
Received: 7 July 2018 / Revised: 21 August 2018 / Accepted: 27 August 2018 / Published: 30 August 2018
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Abstract
For centuries, the development of vaccines to prevent infectious disease was an empirical process. From smallpox variolation in Song dynasty China, through the polysaccharide capsule vaccines developed in the 1970s, vaccines were made either from the pathogen itself, treated in some way to [...] Read more.
For centuries, the development of vaccines to prevent infectious disease was an empirical process. From smallpox variolation in Song dynasty China, through the polysaccharide capsule vaccines developed in the 1970s, vaccines were made either from the pathogen itself, treated in some way to render it attenuated or non-infectious, or from a closely related non-pathogenic strain. In recent decades, new scientific knowledge and technologies have enabled rational vaccine design in a way that was unimaginable before. However, vaccines optimal against some infectious diseases, influenza among them, have remained elusive. This review will highlight the challenges that influenza viruses pose for rational vaccine design. In particular, it will consider the clinically beneficial endpoints, beyond complete sterilizing immunity, that have been achieved with vaccines against other infectious diseases, as well as the barriers to achieving similar success against influenza. Full article
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Open AccessReview Avian Influenza A Virus Pandemic Preparedness and Vaccine Development
Received: 25 June 2018 / Revised: 17 July 2018 / Accepted: 21 July 2018 / Published: 25 July 2018
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Abstract
Influenza A viruses can infect a wide range of hosts, creating opportunities for zoonotic transmission, i.e., transmission from animals to humans, and placing the human population at constant risk of potential pandemics. In the last hundred years, four influenza A virus pandemics have [...] Read more.
Influenza A viruses can infect a wide range of hosts, creating opportunities for zoonotic transmission, i.e., transmission from animals to humans, and placing the human population at constant risk of potential pandemics. In the last hundred years, four influenza A virus pandemics have had a devastating effect, especially the 1918 influenza pandemic that took the lives of at least 40 million people. There is a constant risk that currently circulating avian influenza A viruses (e.g., H5N1, H7N9) will cause a new pandemic. Vaccines are the cornerstone in preparing for and combating potential pandemics. Despite exceptional advances in the design and development of (pre-)pandemic vaccines, there are still serious challenges to overcome, mainly caused by intrinsic characteristics of influenza A viruses: Rapid evolution and a broad host range combined with maintenance in animal reservoirs, making it near impossible to predict the nature and source of the next pandemic virus. Here, recent advances in the development of vaccination strategies to prepare against a pandemic virus coming from the avian reservoir will be discussed. Furthermore, remaining challenges will be addressed, setting the agenda for future research in the development of new vaccination strategies against potentially pandemic influenza A viruses. Full article
Open AccessReview The Role of Fc Gamma Receptors in Broad Protection against Influenza Viruses
Received: 27 May 2018 / Revised: 25 June 2018 / Accepted: 26 June 2018 / Published: 29 June 2018
Cited by 3 | PDF Full-text (1711 KB) | HTML Full-text | XML Full-text
Abstract
Recent studies have revealed multiple roles for Fc gamma receptors (FcγRs) in broad immunity against influenza viruses. Activating FcγR pathways can be harnessed to confer protection mediated by non-neutralizing anti-HA IgGs and to increase the potency of broadly neutralizing anti-HA IgGs and of [...] Read more.
Recent studies have revealed multiple roles for Fc gamma receptors (FcγRs) in broad immunity against influenza viruses. Activating FcγR pathways can be harnessed to confer protection mediated by non-neutralizing anti-HA IgGs and to increase the potency of broadly neutralizing anti-HA IgGs and of anti-NA IgGs. Separate FcγR pathways can be targeted to enhance the breadth of antibody responses elicited by seasonal influenza virus vaccines. Here, we review the current understanding of FcγR pathways in broad influenza immunity and suggest mechanisms to bypass FcγR signaling heterogeneity among people that arises from distinctions in structural repertoires of IgG Fc domains. Full article
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Open AccessReview Clinical Expectations for Better Influenza Virus Vaccines—Perspectives from the Young Investigators’ Point of View
Received: 23 March 2018 / Revised: 23 May 2018 / Accepted: 23 May 2018 / Published: 26 May 2018
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Abstract
The influenza virus is one of a few viruses that is capable of rendering an otherwise healthy person acutly bedridden for several days. This impressive knock-out effect, without prodromal symptoms, challenges our immune system. The influenza virus undergoes continuous mutations, escaping our pre-existing [...] Read more.
The influenza virus is one of a few viruses that is capable of rendering an otherwise healthy person acutly bedridden for several days. This impressive knock-out effect, without prodromal symptoms, challenges our immune system. The influenza virus undergoes continuous mutations, escaping our pre-existing immunity and causing epidemics, and its segmented genome is subject to reassortment, resulting in novel viruses with pandemic potential. The personal and socieoeconomic burden from influenza is high. Vaccination is the most cost-effective countermeasure, with several vaccines that are available. The current limitations in vaccine effectivness, combined with the need for yearly updating of vaccine strains, is a driving force for research into developing new and improved influenza vaccines. The lack of public concern about influenza severity, and misleading information concerning vaccine safety contribute to low vaccination coverage even in high-risk groups. The success of future influeza vaccines will depend on an increased public awarness of the disease, and hence, the need for vaccination—aided through improved rapid diagnositics. The vaccines must be safe and broadly acting, with new, measurable correlates of protection and robust post-marketing safety studies, to improve the confidence in influenza vaccines. Full article
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Open AccessReview Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy
Received: 17 March 2018 / Revised: 11 May 2018 / Accepted: 21 May 2018 / Published: 25 May 2018
Cited by 1 | PDF Full-text (4212 KB) | HTML Full-text | XML Full-text
Abstract
Influenza viruses affect millions of people worldwide on an annual basis. Although vaccines are available, influenza still causes significant human mortality and morbidity. Vaccines target the major influenza surface glycoprotein hemagglutinin (HA). However, circulating HA subtypes undergo continual variation in their dominant epitopes, [...] Read more.
Influenza viruses affect millions of people worldwide on an annual basis. Although vaccines are available, influenza still causes significant human mortality and morbidity. Vaccines target the major influenza surface glycoprotein hemagglutinin (HA). However, circulating HA subtypes undergo continual variation in their dominant epitopes, requiring vaccines to be updated annually. A goal of next-generation influenza vaccine research is to produce broader protective immunity against the different types, subtypes, and strains of influenza viruses. One emerging strategy is to focus the immune response away from variable epitopes, and instead target the conserved stem region of HA. To increase the display and immunogenicity of the HA stem, nanoparticles are being developed to display epitopes in a controlled spatial arrangement to improve immunogenicity and elicit protective immune responses. Engineering of these nanoparticles requires structure-guided design to optimize the fidelity and valency of antigen presentation. Here, we review electron microscopy applied to study the 3D structures of influenza viruses and different vaccine antigens. Structure-guided information from electron microscopy should be integrated into pipelines for the development of both more efficacious seasonal and universal influenza vaccine antigens. The lessons learned from influenza vaccine electron microscopic research could aid in the development of novel vaccines for other pathogens. Full article
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Open AccessReview Clinical Advances in Viral-Vectored Influenza Vaccines
Received: 19 April 2018 / Revised: 21 May 2018 / Accepted: 21 May 2018 / Published: 24 May 2018
Cited by 3 | PDF Full-text (635 KB) | HTML Full-text | XML Full-text
Abstract
Influenza-virus-mediated disease can be associated with high levels of morbidity and mortality, particularly in younger children and older adults. Vaccination is the primary intervention used to curb influenza virus infection, and the WHO recommends immunization for at-risk individuals to mitigate disease. Unfortunately, influenza [...] Read more.
Influenza-virus-mediated disease can be associated with high levels of morbidity and mortality, particularly in younger children and older adults. Vaccination is the primary intervention used to curb influenza virus infection, and the WHO recommends immunization for at-risk individuals to mitigate disease. Unfortunately, influenza vaccine composition needs to be updated annually due to antigenic shift and drift in the viral immunogen hemagglutinin (HA). There are a number of alternate vaccination strategies in current development which may circumvent the need for annual re-vaccination, including new platform technologies such as viral-vectored vaccines. We discuss the different vectored vaccines that have been or are currently in clinical trials, with a forward-looking focus on immunogens that may be protective against seasonal and pandemic influenza infection, in the context of viral-vectored vaccines. We also discuss future perspectives and limitations in the field that will need to be addressed before new vaccines can significantly impact disease levels. Full article
Open AccessReview Immune History and Influenza Vaccine Effectiveness
Received: 28 April 2018 / Revised: 14 May 2018 / Accepted: 16 May 2018 / Published: 21 May 2018
Cited by 10 | PDF Full-text (311 KB) | HTML Full-text | XML Full-text
Abstract
The imperfect effectiveness of seasonal influenza vaccines is often blamed on antigenic mismatch, but even when the match appears good, effectiveness can be surprisingly low. Seasonal influenza vaccines also stand out for their variable effectiveness by age group from year to year and [...] Read more.
The imperfect effectiveness of seasonal influenza vaccines is often blamed on antigenic mismatch, but even when the match appears good, effectiveness can be surprisingly low. Seasonal influenza vaccines also stand out for their variable effectiveness by age group from year to year and by recent vaccination status. These patterns suggest a role for immune history in influenza vaccine effectiveness, but inference is complicated by uncertainty about the contributions of bias to the estimates themselves. In this review, we describe unexpected patterns in the effectiveness of seasonal influenza vaccination and explain how these patterns might arise as consequences of study design, the dynamics of immune memory, or both. Resolving this uncertainty could lead to improvements in vaccination strategy, including the use of universal vaccines in experienced populations, and the evaluation of vaccine efficacy against influenza and other antigenically variable pathogens. Full article
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Open AccessReview “Gnothi Seauton”: Leveraging the Host Response to Improve Influenza Virus Vaccine Efficacy
Received: 2 March 2018 / Revised: 9 April 2018 / Accepted: 10 April 2018 / Published: 12 April 2018
Cited by 2 | PDF Full-text (4782 KB) | HTML Full-text | XML Full-text
Abstract
Vaccination against the seasonal influenza virus is the best way to prevent infection. Nevertheless, vaccine efficacy remains far from optimal especially in high-risk populations such as the elderly. Recent technological advancements have facilitated rapid and precise identification of the B and T cell [...] Read more.
Vaccination against the seasonal influenza virus is the best way to prevent infection. Nevertheless, vaccine efficacy remains far from optimal especially in high-risk populations such as the elderly. Recent technological advancements have facilitated rapid and precise identification of the B and T cell epitopes that are targets for protective responses. While these discoveries have undoubtedly brought the field closer to “universal” influenza virus vaccines, choosing the correct antigen is only one piece of the equation. Achieving efficacy and durability requires a detailed understanding of the diverse host factors and pathways that are required for attaining optimal responses. Sequencing technologies, systems biology, and immunological studies have recently advanced our understanding of the diverse aspects of the host response required for vaccine efficacy. In this paper, we review the critical role of the host response in determining efficacious responses and discuss the gaps in knowledge that will need to be addressed if the field is to be successful in developing new and more effective influenza virus vaccines. Full article
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Open AccessFeature PaperReview New Kids on the Block: RNA-Based Influenza Virus Vaccines
Received: 28 February 2018 / Revised: 21 March 2018 / Accepted: 27 March 2018 / Published: 1 April 2018
Cited by 4 | PDF Full-text (306 KB) | HTML Full-text | XML Full-text
Abstract
RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one [...] Read more.
RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors’ personal perspectives about the future of RNA-based influenza virus vaccines. Full article
Open AccessReview Efforts to Improve the Seasonal Influenza Vaccine
Received: 28 February 2018 / Revised: 26 March 2018 / Accepted: 27 March 2018 / Published: 30 March 2018
Cited by 3 | PDF Full-text (1150 KB) | HTML Full-text | XML Full-text
Abstract
Influenza viruses infect approximately 20% of the global population annually, resulting in hundreds of thousands of deaths. While there are Food and Drug Administration (FDA) approved antiviral drugs for combating the disease, vaccination remains the best strategy for preventing infection. Due to the [...] Read more.
Influenza viruses infect approximately 20% of the global population annually, resulting in hundreds of thousands of deaths. While there are Food and Drug Administration (FDA) approved antiviral drugs for combating the disease, vaccination remains the best strategy for preventing infection. Due to the rapid mutation rate of influenza viruses, vaccine formulations need to be updated every year to provide adequate protection. In recent years, a great amount of effort has been focused on the development of a universal vaccine capable of eliciting broadly protective immunity. While universal influenza vaccines clearly have the best potential to provide long-lasting protection against influenza viruses, the timeline for their development, as well as the true universality of protection they afford, remains uncertain. In an attempt to reduce influenza disease burden while universal vaccines are developed and tested, many groups are working on a variety of strategies to improve the efficacy of the standard seasonal vaccine. This review will highlight the different techniques and technologies that have been, or are being, developed to improve the seasonal vaccination efforts against influenza viruses. Full article
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Open AccessReview Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine
Received: 28 February 2018 / Revised: 21 March 2018 / Accepted: 21 March 2018 / Published: 26 March 2018
Cited by 8 | PDF Full-text (10584 KB) | HTML Full-text | XML Full-text
Abstract
Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide [...] Read more.
Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm), population human leucocyte antigen (HLA) coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods. Current pandemic vaccine preparedness measures and ongoing clinical trials under-utilise T cell-inducing vaccines, reflecting the myriad questions that remain about how, when, where, and which T cells are needed to fight influenza virus infection. This review aims to bring together basic fundamentals of T cell biology with human clinical data, which need to be considered for the implementation of a universal vaccine against influenza that harnesses the power of T cells. Full article
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Open AccessReview Epidemiological Studies to Support the Development of Next Generation Influenza Vaccines
Received: 2 March 2018 / Revised: 21 March 2018 / Accepted: 21 March 2018 / Published: 26 March 2018
Cited by 1 | PDF Full-text (264 KB) | HTML Full-text | XML Full-text
Abstract
The National Institute of Allergy and Infectious Diseases recently published a strategic plan for the development of a universal influenza vaccine. This plan focuses on improving understanding of influenza infection, the development of influenza immunity, and rational design of new vaccines. Epidemiological studies [...] Read more.
The National Institute of Allergy and Infectious Diseases recently published a strategic plan for the development of a universal influenza vaccine. This plan focuses on improving understanding of influenza infection, the development of influenza immunity, and rational design of new vaccines. Epidemiological studies such as prospective, longitudinal cohort studies are essential to the completion of these objectives. In this review, we discuss the contributions of epidemiological studies to our current knowledge of vaccines and correlates of immunity, and how they can contribute to the development and evaluation of the next generation of influenza vaccines. These studies have been critical in monitoring the effectiveness of current influenza vaccines, identifying issues such as low vaccine effectiveness, reduced effectiveness among those who receive repeated vaccination, and issues related to egg adaptation during the manufacturing process. Epidemiological studies have also identified population-level correlates of protection that can inform the design and development of next generation influenza vaccines. Going forward, there is an enduring need for epidemiological studies to continue advancing knowledge of correlates of protection and the development of immunity, to evaluate and monitor the effectiveness of next generation influenza vaccines, and to inform recommendations for their use. Full article

Other

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Open AccessPerspective Immunizing the Immune: Can We Overcome Influenza’s Most Formidable Challenge?
Received: 17 August 2018 / Revised: 16 September 2018 / Accepted: 18 September 2018 / Published: 22 September 2018
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Abstract
The first human influenza virus was isolated more than 85 years ago, and several vaccine candidates were developed and tested soon after. Yet, controlling infections mediated by this respiratory pathogen continues to present a formidable challenge. Development of an effective influenza vaccine has [...] Read more.
The first human influenza virus was isolated more than 85 years ago, and several vaccine candidates were developed and tested soon after. Yet, controlling infections mediated by this respiratory pathogen continues to present a formidable challenge. Development of an effective influenza vaccine has been undermined by the dynamic nature of influenza viruses: these viruses have the unique capacity to escape pre-existing immunity. In this perspective, I highlight pre-existing immunity as a different, but related, hurdle that may actually lessen the effectiveness of influenza vaccine-induced immune responses. Specifically, I discuss the impact of pre-existing immunity on the generation of de novo B cell responses to influenza vaccination. As the influenza virus changes its major antigenic determinants, it creates new ones in the process. Our immune system adapts by targeting the new determinants. However, pre-existing antibodies and memory B cells interfere with the generation of de novo responses against these newly formed epitopes, rendering vaccines less effective. Overcoming such interference is essential for the development of more effective influenza vaccines. Full article
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Open AccessPerspective The Potential Role of Fc-Receptor Functions in the Development of a Universal Influenza Vaccine
Received: 9 April 2018 / Revised: 8 May 2018 / Accepted: 10 May 2018 / Published: 17 May 2018
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Abstract
Despite global vaccination efforts, influenza virus continues to cause yearly epidemics and periodic pandemics throughout most of the world. Many of us consider the generation of broader, potent and long-lasting immunity against influenza viruses as critical in curtailing the global health and economic [...] Read more.
Despite global vaccination efforts, influenza virus continues to cause yearly epidemics and periodic pandemics throughout most of the world. Many of us consider the generation of broader, potent and long-lasting immunity against influenza viruses as critical in curtailing the global health and economic impact that influenza currently plays. To date, classical vaccinology has relied on the generation of neutralizing antibodies as the benchmark to measure vaccine effectiveness. However, recent developments in numerous related fields of biomedical research including, HIV, HSV and DENV have emphasized the importance of Fc-mediate effector functions in pathogenesis and immunity. The concept of Fc effector functions in contributing to protection from illness is not a new concept and has been investigated in the field for over four decades. However, in recent years the application and study of Fc effector functions has become revitalized with new knowledge and technologies to characterize their potential importance in immunity. In this perspective, we describe the current state of the field of Influenza Fc effector functions and discuss its potential utility in universal vaccine design in the future. Full article
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Open AccessPerspective Development and Regulation of Novel Influenza Virus Vaccines: A United States Young Scientist Perspective
Received: 4 April 2018 / Revised: 20 April 2018 / Accepted: 25 April 2018 / Published: 27 April 2018
Cited by 1 | PDF Full-text (199 KB) | HTML Full-text | XML Full-text
Abstract
Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy [...] Read more.
Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy of each selected influenza virus vaccine varies depending on the antigenic match between circulating strains and vaccine strains, as well as the age and health status of the vaccine recipient. Low vaccine effectiveness of seasonal influenza vaccines in recent years provides an impetus to improve current seasonal influenza vaccines, and for development of next-generation influenza vaccines that can provide broader, long-lasting protection against both matching and antigenically diverse influenza strains. This review discusses a perspective on some of the issues and formidable challenges facing the development and regulation of the next-generation influenza vaccines. Full article
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