CD8+ T-cell responses in vaccination: reconsidering targets and function in the context of chronic antigen stimulation

Cytotoxic CD8 T cells play important roles in eliminating infected and transformed cells. Owing to their potential for therapeutic applications, significant efforts are dedicated toward developing CD8 T cell–based vaccines. Thus far, CD8 T-cell vaccination strategies have had limited success therapeutically in contrast to those targeting antibody-based immunity. However, if the current challenges and gaps in the understanding of T-cell biology are overcome, the full potential of rational CD8 T-cell vaccine design might be realized. Here, we review recent progress in this direction, focusing on target selection and maintenance of function in the settings of chronic infections and cancers.

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Is a Human CD8 T-Cell Vaccine Possible, and if So, What Would It Take?

Cold Spring Harbor Perspectives in Biology ◽

10.1101/cshperspect.a028910 ◽

2017 ◽

Vol 10 (9) ◽

pp. a028910 ◽

Cited By ~ 3

Author(s):

Lalit K. Beura ◽

Stephen C. Jameson ◽

David Masopust

Keyword(s):

T Cell ◽

Cd8 T Cell ◽

Cell Vaccine ◽

T Cell Vaccine

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Biopolymer encapsulated live influenza virus as a universal CD8+ T cell vaccine against influenza virus

Vaccine ◽

10.1016/j.vaccine.2010.10.036 ◽

2010 ◽

Vol 29 (2) ◽

pp. 314-322 ◽

Cited By ~ 6

Author(s):

Alina C. Boesteanu ◽

Nadarajan S. Babu ◽

Margaret Wheatley ◽

Elisabeth S. Papazoglou ◽

Peter D. Katsikis

Keyword(s):

Influenza Virus ◽

T Cell ◽

Cd8 T Cell ◽

Cell Vaccine ◽

T Cell Vaccine

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Utilizing Computational Machine Learning Tools to Understand Immunogenic Breadth in the Context of a CD8 T-Cell Mediated HIV Response

10.1101/2020.08.15.250589 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ed McGowan ◽

Rachel Rosenthal ◽

Andrew Fiore-Gartland ◽

Gladys Macharia ◽

Sheila Balinda ◽

...

Keyword(s):

T Cell ◽

Vaccine Design ◽

Cd8 T Cell ◽

Cell Vaccine ◽

Learning Tools ◽

T Cell Vaccine ◽

Novel Approach ◽

Low Prevalence ◽

Global And Local

ABSTRACTPredictive models are becoming more and more commonplace as tools for candidate antigen discovery to meet the challenges of enabling epitope mapping of cohorts with diverse HLA properties. Here we build on the concept of using two key parameters, diversity metric of the HLA profile of individuals within a population and consideration of sequence diversity in the context of an individual’s CD8 T-cell immune repertoire to assess the HIV proteome for defined regions of immunogenicity. Using this approach, Analysis of HLA adaptation and functional immunogenicity data enabled the identification of regions within the proteome that offer significant conservation, HLA recognition within a population, low prevalence of HLA adaptation and demonstrated immunogenicity. We believe this unique and novel approach to vaccine design that, in combination with in vitro functional assays, offers a bespoke pipeline for expedited and rational CD8 T-cell vaccine design for HIV and potentially other pathogens with the potential for both global and local coverage.

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An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design

10.1101/2020.02.25.963546 ◽

2020 ◽

Cited By ~ 7

Author(s):

CV Herst ◽

S Burkholz ◽

J Sidney ◽

A Sette ◽

PE Harris ◽

...

Keyword(s):

T Cell ◽

Nucleocapsid Protein ◽

Peptide Vaccine ◽

Vaccine Design ◽

Cd8 T Cell ◽

T Cell Immunity ◽

Cell Vaccine ◽

Amino Acid Peptide ◽

T Cell Vaccine ◽

Cell Immunity

AbstractThe 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.

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Sampling SARS-CoV-2 Proteomes for Predicted CD8 T-Cell Epitopes as a Tool for Understanding Immunogenic Breadth and Rational Vaccine Design

Frontiers in Bioinformatics ◽

10.3389/fbinf.2021.622992 ◽

2021 ◽

Vol 1 ◽

Author(s):

Jonathan Hare ◽

David Morrison ◽

Morten Nielsen

Keyword(s):

T Cell ◽

Therapeutic Vaccine ◽

Vaccine Design ◽

Cd8 T Cell ◽

Cell Vaccine ◽

T Cell Epitopes ◽

Global Pandemic ◽

T Cell Vaccine ◽

Rational Vaccine Design ◽

Global And Local

Predictive models for vaccine design have become a powerful and necessary resource for the expeditiousness design of vaccines to combat the ongoing SARS-CoV-2 global pandemic. Here we use the power of these predicted models to assess the sequence diversity of circulating SARS-CoV-2 proteomes in the context of an individual’s CD8 T-cell immune repertoire to identify potential. defined regions of immunogenicity. Using this approach of expedited and rational CD8 T-cell vaccine design, it may be possible to develop a therapeutic vaccine candidate with the potential for both global and local coverage.

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