Special Issue "T Cell Memory to Vaccination"

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

Deadline for manuscript submissions: closed (30 June 2018).

Special Issue Editor

Prof. Dr. Stephen Todryk
E-Mail Website
Guest Editor
Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, UK; and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
Interests: T cells; anti-microbial immunity; immune memory; biomarkers
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Since it is at the heart of vaccination, the continuing growth in the understanding of T cell memory will enhance the development of vaccines. This special issue of Vaccines is aimed at reviewing the various ways in which T cell memory may impact upon the immunogenicity, and ultimately the efficacy, of vaccines that are widely used or in development. Many vaccines in use today continue to rely on old manufacturing technology and are far from optimal in their efficacy. The target populations to vaccinate are usually at extremes of age, and often have some deficiencies in immune responses, requiring vaccines and vaccine regimens that deliver frequent, high doses of antigen. Several diseases have no available vaccines that prevent (or treat) them, such as malaria, HIV, Hepatitis C, and cancers. However, a novel meningococcal B vaccine has recently been licensed, and a malaria vaccine is close. Antibodies have conventionally been the desired outcome of vaccination, and their measurement a marker of protection. Many new vaccines are also targeting T cell responses that either help the antibody response or have direct effector functions themselves. These vaccines include conjugate vaccines, recombinant antigens in adjuvants, and recombinant antigen-encoding viruses. Resulting antigen-specific T cell responses need to be of the appropriate T-helper subtype, memory and homing phenotype, and not be exhausted via immune checkpoints. Ultimately, a correct formulation and regimen (including route of vaccination [e.g. mucosal] and boosting) will be required that generates this appropriate T cell phenotype. Measurement of these T cells will provide useful markers of efficacy. They may or may not imitate the protective T cell responses generated in natural immunity. Innate immunity also impinges on the vaccine-induced priming process, and effector lymphocytes with invariant T cell receptors are likely to be involved. Thus, a highly integrated approach to vaccine design is unavoidable, and will be discussed in this edition of the journal.

Professor Dr. Stephen Todryk
Guest Editor

Manuscript Submission Information

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Keywords

  • T cells

  • immune memory

  • T cell subtypes

  • vaccination

Published Papers (8 papers)

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Editorial

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Open AccessEditorial
T Cell Memory to Vaccination
Vaccines 2018, 6(4), 84; https://doi.org/10.3390/vaccines6040084 - 14 Dec 2018
Cited by 2
Abstract
Most immune responses associated with vaccination are controlled by specific T cells of a CD4+ helper phenotype which mediate the generation of effector antibodies, cytotoxic T lymphocytes (CTLs), or the activation of innate immune effector cells. A rapidly growing understanding of the [...] Read more.
Most immune responses associated with vaccination are controlled by specific T cells of a CD4+ helper phenotype which mediate the generation of effector antibodies, cytotoxic T lymphocytes (CTLs), or the activation of innate immune effector cells. A rapidly growing understanding of the generation, maintenance, activity, and measurement of such T cells is leading to vaccination strategies with greater efficacy and potentially greater microbial coverage. Full article
(This article belongs to the Special Issue T Cell Memory to Vaccination)

Research

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Open AccessArticle
Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials
Vaccines 2018, 6(3), 50; https://doi.org/10.3390/vaccines6030050 - 31 Jul 2018
Cited by 3
Abstract
Immunogenicity of T cell-inducing vaccines, such as viral vectors or DNA vaccines and Bacillus Calmette-Guérin (BCG), are frequently assessed by cytokine-based approaches. While these are sensitive methods that have shown correlates of protection in various vaccine studies, they only identify a small proportion [...] Read more.
Immunogenicity of T cell-inducing vaccines, such as viral vectors or DNA vaccines and Bacillus Calmette-Guérin (BCG), are frequently assessed by cytokine-based approaches. While these are sensitive methods that have shown correlates of protection in various vaccine studies, they only identify a small proportion of the vaccine-specific T cell response. Responses to vaccination are likely to be heterogeneous, particularly when comparing prime and boost or assessing vaccine performance across diverse populations. Activation-induced markers (AIM) can provide a broader view of the total antigen-specific T cell response to enable a more comprehensive evaluation of vaccine immunogenicity. We tested an AIM assay for the detection of vaccine-specific CD4+ and CD8+ T cell responses in healthy UK adults vaccinated with viral vectored Ebola vaccine candidates, ChAd3-EBO-Z and MVA-EBO-Z. We used the markers, CD25, CD134 (OX40), CD274 (PDL1), and CD107a, to sensitively identify vaccine-responsive T cells. We compared the use of OX40+CD25+ and OX40+PDL1+ in CD4+ T cells and OX40+CD25+ and CD25+CD107a+ in CD8+ T cells for their sensitivity, specificity, and associations with other measures of vaccine immunogenicity. We show that activation-induced markers can be used as an additional method of demonstrating vaccine immunogenicity, providing a broader picture of the global T cell response to vaccination. Full article
(This article belongs to the Special Issue T Cell Memory to Vaccination)
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Open AccessArticle
Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection
Vaccines 2016, 4(3), 27; https://doi.org/10.3390/vaccines4030027 - 02 Aug 2016
Cited by 10
Abstract
An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A [...] Read more.
An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy), determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression) compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T-cells were only induced by vaccination when there was a sequence mismatch between the autologous virus and the vaccine immunogen. However, these T-cells were not cross-reactive with the endogenous viral variant epitopes. Conversely, when there was complete homology between the immunogen and circulating virus at a given epitope T-cells were not induced. T-cell induction following vaccination had no significant impact on HCV viral load. In vitro T-cell culture experiments identified the presence of T-cells at baseline that could be expanded by vaccination; thus, HCV-specific T-cells may have been expanded from pre-existing low-level memory T-cell populations that had been exposed to HCV antigens during natural infection, explaining the partial T-cell dysfunction. In conclusion, vaccination with ChAd3-NSmut and MVA-NSmut prime/boost, a potent vaccine regimen previously optimized in healthy volunteers was unable to reconstitute HCV-specific T-cell immunity in HCV infected patients. This highlights the major challenge of overcoming T-cell exhaustion in the context of persistent antigen exposure. Full article
(This article belongs to the Special Issue T Cell Memory to Vaccination)
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Review

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Open AccessReview
Memory T Cells in Flavivirus Vaccination
Vaccines 2018, 6(4), 73; https://doi.org/10.3390/vaccines6040073 - 18 Oct 2018
Cited by 5
Abstract
Flaviviruses include many medically important viruses, such as Dengue virus (DENV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), West Nile (WNV), yellow fever (YFV), and Zika viruses (ZIKV). Currently, there are licensed human vaccines for DENV, JEV, TBEV and YFV, but not for WNV [...] Read more.
Flaviviruses include many medically important viruses, such as Dengue virus (DENV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), West Nile (WNV), yellow fever (YFV), and Zika viruses (ZIKV). Currently, there are licensed human vaccines for DENV, JEV, TBEV and YFV, but not for WNV or ZIKV. Memory T cells play a central role in adaptive immunity and are important for host protection during flavivirus infection. In this review, we discuss recent findings from animal models and clinical trials and provide new insights into the role of memory T cells in host protective immunity upon vaccination with the licensed flavivirus vaccines. Full article
(This article belongs to the Special Issue T Cell Memory to Vaccination)
Open AccessReview
Methods for Measuring T-Cell Memory to Vaccination: From Mouse to Man
Vaccines 2018, 6(3), 43; https://doi.org/10.3390/vaccines6030043 - 21 Jul 2018
Cited by 3
Abstract
The development of effective vaccines continues to be a key goal for public health bodies, governments, funding bodies and pharmaceutical companies. With new vaccines such as Shingrix targeting Shingles and Bexsero for Meningitis B, licensed in recent years, today’s population can be protected [...] Read more.
The development of effective vaccines continues to be a key goal for public health bodies, governments, funding bodies and pharmaceutical companies. With new vaccines such as Shingrix targeting Shingles and Bexsero for Meningitis B, licensed in recent years, today’s population can be protected from more infectious diseases than ever before. Despite this, we are yet to license vaccines for some of the deadliest endemic diseases affecting children, such as malaria. In addition, the threat of epidemics caused by emerging pathogens is very real as exemplified by the 2014–2016 Ebola outbreak. Most licensed vaccines provide efficacy through humoral immunity and correlates of protection often quantify neutralising antibody titre. The role of T-cells in vaccine efficacy is less well understood and more complex to quantify. Defining T-cell responses which afford protection also remains a challenge, although more sophisticated assays for assessing cell-mediated immunity with the potential for higher throughput and scalability are now available and warrant review. Here we discuss the benefits of multiparameter cytokine analysis and omics approaches compared with flow cytometric and ELISpot assays. We also review technical challenges unique to clinical trial studies, including assay validation across laboratories and availability of sample type. Measuring T-cell immunogenicity alongside humoral responses provides information on the breadth of immune responses induced by vaccination. Accurately enumerating and phenotyping T-cell immunogenicity to vaccination is key for the determination of immune correlates of protection. However, identifying such T-cell parameters remains challenging without a clear understanding of the immunological mechanisms by which a T-cell-mediated response induces protection. Full article
(This article belongs to the Special Issue T Cell Memory to Vaccination)
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Open AccessReview
Human T Cell Memory: A Dynamic View
Vaccines 2017, 5(1), 5; https://doi.org/10.3390/vaccines5010005 - 04 Feb 2017
Cited by 14
Abstract
Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are [...] Read more.
Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy. Full article
(This article belongs to the Special Issue T Cell Memory to Vaccination)
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Open AccessReview
Influenza and Memory T Cells: How to Awake the Force
Vaccines 2016, 4(4), 33; https://doi.org/10.3390/vaccines4040033 - 13 Oct 2016
Cited by 9
Abstract
Annual influenza vaccination is an effective way to prevent human influenza. Current vaccines are mainly focused on eliciting a strain-matched humoral immune response, requiring yearly updates, and do not provide protection for all vaccinated individuals. The past few years, the importance of cellular [...] Read more.
Annual influenza vaccination is an effective way to prevent human influenza. Current vaccines are mainly focused on eliciting a strain-matched humoral immune response, requiring yearly updates, and do not provide protection for all vaccinated individuals. The past few years, the importance of cellular immunity, and especially memory T cells, in long-lived protection against influenza virus has become clear. To overcome the shortcomings of current influenza vaccines, eliciting both humoral and cellular immunity is imperative. Today, several new vaccines such as infection-permissive and recombinant T cell inducing vaccines, are being developed and show promising results. These vaccines will allow us to stay several steps ahead of the constantly evolving influenza virus. Full article
(This article belongs to the Special Issue T Cell Memory to Vaccination)
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Open AccessReview
T-Regulatory Cells and Vaccination “Pay Attention and Do Not Neglect Them”: Lessons from HIV and Cancer Vaccine Trials
Vaccines 2016, 4(3), 30; https://doi.org/10.3390/vaccines4030030 - 05 Sep 2016
Cited by 8
Abstract
Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory [...] Read more.
Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory conditions is ambiguous and their systematic monitoring in vaccination along with effector T-cells is not instinctive. Recent studies from the cancer field clearly showed that Tregs suppress vaccine-induced immune responses and correlate with poor clinical benefit. In HIV infection, Tregs are needed during acute infection to preserve tissue integrity from an overwhelmed activation, but are not beneficial in chronic infection as they suppress anti-HIV responses. Current assays used to evaluate vaccine-induced specific responses are limited as they do not take into account antigen-specific Tregs. However, new assays, such as the OX40 assay, which allow for the simultaneous detection of a full range of Th-responses including antigen-specific Tregs responses, can overcome these issues. In this review article we will revise the role of Tregs in vaccination and review the recent work performed in the field, including the available tools to monitor them, from novel assays to humanized mouse models. Full article
(This article belongs to the Special Issue T Cell Memory to Vaccination)
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