Vaccines

13 pages, 534 KiB

Open AccessReview

Postgenomic Approaches and Bioinformatics Tools to Advance the Development of Vaccines against Bacteria of the Burkholderia cepacia Complex

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

Vaccines 2018, 6(2), 34; https://doi.org/10.3390/vaccines6020034 - 8 Jun 2018

Cited by 8 | Viewed by 5752

Abstract

Bacteria of the Burkholderia cepacia complex (Bcc) remain an important cause of morbidity and mortality among patients suffering from cystic fibrosis. Eradication of these pathogens by antimicrobial therapy often fails, highlighting the need to develop novel strategies to eradicate infections. Vaccines are attractive [...] Read more.

Bacteria of the Burkholderia cepacia complex (Bcc) remain an important cause of morbidity and mortality among patients suffering from cystic fibrosis. Eradication of these pathogens by antimicrobial therapy often fails, highlighting the need to develop novel strategies to eradicate infections. Vaccines are attractive since they can confer protection to particularly vulnerable patients, as is the case of cystic fibrosis patients. Several studies have identified specific virulence factors and proteins as potential subunit vaccine candidates. So far, no vaccine is available to protect from Bcc infections. In the present work, we review the most promising postgenomic approaches and selected web tools available to speed up the identification of immunogenic proteins with the potential of conferring protection against Bcc infections. Full article

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2 pages, 133 KiB

Open AccessEditorial

What’s Fair Is Fair: Leveling the Playing Field for Young Scientists

by Jonathan W. Yewdell

Vaccines 2018, 6(2), 33; https://doi.org/10.3390/vaccines6020033 - 31 May 2018

Cited by 1 | Viewed by 3943

Abstract

Like every MD Ph.D. pup, I was faced with the BIG decision: medicine or science?[...] Full article

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

16 pages, 1280 KiB

Open AccessReview

Clinical Expectations for Better Influenza Virus Vaccines—Perspectives from the Young Investigators’ Point of View

by Kristin G.-I. Mohn and Fan Zhou

Vaccines 2018, 6(2), 32; https://doi.org/10.3390/vaccines6020032 - 26 May 2018

Cited by 6 | Viewed by 7885

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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21 pages, 4212 KiB

Open AccessReview

Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy

by John R. Gallagher, Dustin M. McCraw, Udana Torian, Neetu M. Gulati, Mallory L. Myers, Michael T. Conlon and Audray K. Harris

Vaccines 2018, 6(2), 31; https://doi.org/10.3390/vaccines6020031 - 25 May 2018

Cited by 21 | Viewed by 10535

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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17 pages, 2784 KiB

Open AccessArticle

Enhanced Anti-Mycobacterium tuberculosis Immunity over Time with Combined Drug and Immunotherapy Treatment

by Sasha E. Larsen, Susan L. Baldwin, Mark T. Orr, Valerie A. Reese, Tiffany Pecor, Brian Granger, Natasha Dubois Cauwelaert, Brendan K. Podell and Rhea N. Coler

Vaccines 2018, 6(2), 30; https://doi.org/10.3390/vaccines6020030 - 24 May 2018

Cited by 23 | Viewed by 5861

Abstract

It is estimated that one third of the world’s population is infected with Mycobacterium tuberculosis (Mtb). This astounding statistic, in combination with costly and lengthy treatment regimens make the development of therapeutic vaccines paramount for controlling the global burden of tuberculosis. [...] Read more.

It is estimated that one third of the world’s population is infected with Mycobacterium tuberculosis (Mtb). This astounding statistic, in combination with costly and lengthy treatment regimens make the development of therapeutic vaccines paramount for controlling the global burden of tuberculosis. Unlike prophylactic vaccination, therapeutic immunization relies on the natural pulmonary infection with Mtb as the mucosal prime that directs boost responses back to the lung. The purpose of this work was to determine the protection and safety profile over time following therapeutic administration of our lead Mtb vaccine candidate, ID93 with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE)), in combination with rifampicin, isoniazid, and pyrazinamide (RHZ) drug treatment. We assessed the host inflammatory immune responses and lung pathology 7–22 weeks post infection, and determined the therapeutic efficacy of combined treatment by enumeration of the bacterial load and survival in the SWR/J mouse model. We show that drug treatment alone, or with immunotherapy, tempered the inflammatory responses measured in brochoalveolar lavage fluid and plasma compared to untreated cohorts. RHZ combined with therapeutic immunizations significantly enhanced TH1-type cytokine responses in the lung over time, corresponding to decreased pulmonary pathology evidenced by a significant decrease in the percentage of lung lesions and destructive lung inflammation. These data suggest that bacterial burden assessment alone may miss important correlates of lung architecture that directly contribute to therapeutic vaccine efficacy in the preclinical mouse model. We also confirmed our previous finding that in combination with antibiotics therapeutic immunizations provide an additive survival advantage. Moreover, therapeutic immunizations with ID93/GLA-SE induced differential T cell immune responses over the course of infection that correlated with periods of enhanced bacterial control over that of drug treatment alone. Here we advance the immunotherapy model and investigate reliable correlates of protection and Mtb control. Full article

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18 pages, 635 KiB

Open AccessReview

Clinical Advances in Viral-Vectored Influenza Vaccines

by Sarah Sebastian and Teresa Lambe

Vaccines 2018, 6(2), 29; https://doi.org/10.3390/vaccines6020029 - 24 May 2018

Cited by 38 | Viewed by 6428

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

14 pages, 311 KiB

Open AccessReview

Immune History and Influenza Vaccine Effectiveness

by Joseph A. Lewnard and Sarah Cobey

Vaccines 2018, 6(2), 28; https://doi.org/10.3390/vaccines6020028 - 21 May 2018

Cited by 141 | Viewed by 23863

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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17 pages, 612 KiB

Open AccessPerspective

The Potential Role of Fc-Receptor Functions in the Development of a Universal Influenza Vaccine

by Sinthujan Jegaskanda

Vaccines 2018, 6(2), 27; https://doi.org/10.3390/vaccines6020027 - 17 May 2018

Cited by 20 | Viewed by 5251

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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1 pages, 157 KiB

Open AccessCorrection

Correction: Vitetta, L.; et al. Adjuvant Probiotics and the Intestinal Microbiome: Enhancing Vaccines and Immunotherapy Outcomes. Vaccines 2017, 5, 50

by Luis Vitetta, Emma Tali Saltzman, Michael Thomsen, Tessa Nikov and Sean Hall

Vaccines 2018, 6(2), 26; https://doi.org/10.3390/vaccines6020026 - 15 May 2018

Cited by 4 | Viewed by 2908

Abstract

The authors wish to make the following corrections to this paper due to a typesetting error in the conclusion of this article which was recently published in Vaccines[...] Full article

5 pages, 204 KiB

Open AccessComment

Should UK Pneumococcal Vaccine Eligibility Criteria Include Alcohol Dependency in Areas with High Alcohol-Related Mortality?

by John D. Mooney, Michael Imarhiagbe and Jonathan Ling

Vaccines 2018, 6(2), 25; https://doi.org/10.3390/vaccines6020025 - 2 May 2018

Cited by 1 | Viewed by 4563

Abstract

A recently reported steep increase in the incidence of invasive pneumococcal disease (IPD) in adults in the North East of England was primarily associated with pneumococcal sero-types found in the 23-valent pneumococcal polysaccharide vaccine (PPSV23). This region also has one of the highest [...] Read more.

A recently reported steep increase in the incidence of invasive pneumococcal disease (IPD) in adults in the North East of England was primarily associated with pneumococcal sero-types found in the 23-valent pneumococcal polysaccharide vaccine (PPSV23). This region also has one of the highest rates of alcohol-related premature mortality and morbidity in the UK. Given that alcohol dependence is long acknowledged as one of the strongest risk factors for IPD mortality, we feel there is an increasingly compelling case to look again at the divergence of UK vaccine guidance from that of the World Health Organisation and the Centre for Disease Control in the USA, in the non-inclusion of alcoholism as an indicator condition that would potentially benefit from receiving PPSV23 vaccine. Such a re-think would represent a responsible evaluation of vaccination guidance in the face of newly emerging epidemiological findings and would have the potential to save lives in a very marginalised and vulnerable section of the population. We propose therefore that alcohol dependency (now referred to as alcohol use disorder), should be re-considered an indicator condition for receiving pneumococcal vaccine in North East England, where mortality from pneumococcal disease has been rising and which already has an excessive burden of alcohol-related mortality. Full article

10 pages, 199 KiB

Open AccessPerspective

Development and Regulation of Novel Influenza Virus Vaccines: A United States Young Scientist Perspective

by Surender Khurana

Vaccines 2018, 6(2), 24; https://doi.org/10.3390/vaccines6020024 - 27 Apr 2018

Cited by 12 | Viewed by 6203

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

12 pages, 4782 KiB

Open AccessReview

“Gnothi Seauton”: Leveraging the Host Response to Improve Influenza Virus Vaccine Efficacy

by Hannah D. Stacey, Neda Barjesteh, Jonathan P. Mapletoft and Matthew S. Miller

Vaccines 2018, 6(2), 23; https://doi.org/10.3390/vaccines6020023 - 12 Apr 2018

Cited by 9 | Viewed by 5573

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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11 pages, 247 KiB

Open AccessArticle

Predictors and Barriers to Full Vaccination among Children in Ethiopia

by Yemesrach A. Tefera, Abram L. Wagner, Eyoel B. Mekonen, Bradley F. Carlson and Matthew L. Boulton

Vaccines 2018, 6(2), 22; https://doi.org/10.3390/vaccines6020022 - 10 Apr 2018

Cited by 51 | Viewed by 6860

Abstract

Predictors of immunization status outside of large cities in Ethiopia are not well known, and Muslims have lower vaccination coverage. The aim of this study is to assess factors associated with full immunization among children 12–23 months in Worabe, Ethiopia, a Muslim-majority community. [...] Read more.

Predictors of immunization status outside of large cities in Ethiopia are not well known, and Muslims have lower vaccination coverage. The aim of this study is to assess factors associated with full immunization among children 12–23 months in Worabe, Ethiopia, a Muslim-majority community. A cross-sectional study is conducted in summer 2016. Multivariable logistic regression was used to assess the significance of predictors of full immunization. Among 484 children, 61% are fully vaccinated. Children whose mothers had fewer antenatal care (ANC) visits have decreased odds of full vaccination (zero visits: odds ratio (OR) = 0.09; one visit: OR = 0.15; two visits: OR = 0.46; three visits: OR = 0.89). The most common reasons that the mother gave for not vaccinating the child are fear of side reactions (36%), being too busy (31%), or hearing rumors about vaccines (28%). Local interventions incorporating interventions with religious authorities could raise awareness in the community of the importance of childhood immunizations and ANC visits. Full article

27 pages, 1478 KiB

Open AccessReview

Linkage of Infection to Adverse Systemic Complications: Periodontal Disease, Toll-Like Receptors, and Other Pattern Recognition Systems

by Shannon M. Wallet, Vishwajeet Puri and Frank C. Gibson

Vaccines 2018, 6(2), 21; https://doi.org/10.3390/vaccines6020021 - 5 Apr 2018

Cited by 46 | Viewed by 8172

Abstract

Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) that provide innate immune sensing of conserved pathogen-associated molecular patterns (PAMPs) to engage early immune recognition of bacteria, viruses, and protozoa. Furthermore, TLRs provide a conduit for initiation of non-infectious inflammation following [...] Read more.

Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) that provide innate immune sensing of conserved pathogen-associated molecular patterns (PAMPs) to engage early immune recognition of bacteria, viruses, and protozoa. Furthermore, TLRs provide a conduit for initiation of non-infectious inflammation following the sensing of danger-associated molecular patterns (DAMPs) generated as a consequence of cellular injury. Due to their essential role as DAMP and PAMP sensors, TLR signaling also contributes importantly to several systemic diseases including cardiovascular disease, diabetes, and others. The overlapping participation of TLRs in the control of infection, and pathogenesis of systemic diseases, has served as a starting point for research delving into the poorly defined area of infection leading to increased risk of various systemic diseases. Although conflicting studies exist, cardiovascular disease, diabetes, cancer, rheumatoid arthritis, and obesity/metabolic dysfunction have been associated with differing degrees of strength to infectious diseases. Here we will discuss elements of these connections focusing on the contributions of TLR signaling as a consequence of bacterial exposure in the context of the oral infections leading to periodontal disease, and associations with metabolic diseases including atherosclerosis and type 2 diabetes. Full article

(This article belongs to the Special Issue TLR signaling in Immune Response)

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15 pages, 306 KiB

Open AccessFeature PaperReview

New Kids on the Block: RNA-Based Influenza Virus Vaccines

by Francesco Berlanda Scorza and Norbert Pardi

Vaccines 2018, 6(2), 20; https://doi.org/10.3390/vaccines6020020 - 1 Apr 2018

Cited by 70 | Viewed by 15471

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

12 pages, 1150 KiB

Open AccessReview

Efforts to Improve the Seasonal Influenza Vaccine

by Alfred T. Harding and Nicholas S. Heaton

Vaccines 2018, 6(2), 19; https://doi.org/10.3390/vaccines6020019 - 30 Mar 2018

Cited by 93 | Viewed by 18478

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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30 pages, 10584 KiB

Open AccessReview

Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

by E. Bridie Clemens, Carolien Van de Sandt, Sook San Wong, Linda M. Wakim and Sophie A. Valkenburg

Vaccines 2018, 6(2), 18; https://doi.org/10.3390/vaccines6020018 - 26 Mar 2018

Cited by 94 | Viewed by 13124

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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11 pages, 264 KiB

Open AccessReview

Epidemiological Studies to Support the Development of Next Generation Influenza Vaccines

by Joshua G. Petrie and Aubree Gordon

Vaccines 2018, 6(2), 17; https://doi.org/10.3390/vaccines6020017 - 26 Mar 2018

Cited by 12 | Viewed by 5544

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

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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Vaccines, Volume 6, Issue 2 (June 2018) – 18 articles

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