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Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes

HCMV vaccine development has traditionally focused on viral antigens identified as key targets of neutralizing antibody (NAb) and/or T cell responses in healthy adults with chronic HCMV infection, such as glycoprotein B (gB), the glycoprotein H-anchored pentamer complex (PC), and the unique long 83...

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Autores principales: Barry, Peter A., Iyer, Smita S., Gibson, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674879/
https://www.ncbi.nlm.nih.gov/pubmed/38005961
http://dx.doi.org/10.3390/vaccines11111629
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author Barry, Peter A.
Iyer, Smita S.
Gibson, Laura
author_facet Barry, Peter A.
Iyer, Smita S.
Gibson, Laura
author_sort Barry, Peter A.
collection PubMed
description HCMV vaccine development has traditionally focused on viral antigens identified as key targets of neutralizing antibody (NAb) and/or T cell responses in healthy adults with chronic HCMV infection, such as glycoprotein B (gB), the glycoprotein H-anchored pentamer complex (PC), and the unique long 83 (UL83)-encoded phosphoprotein 65 (pp65). However, the protracted absence of a licensed HCMV vaccine that reduces the risk of infection in pregnancy regardless of serostatus warrants a systematic reassessment of assumptions informing vaccine design. To illustrate this imperative, we considered the hypothesis that HCMV proteins infrequently detected as targets of T cell responses may contain important vaccine antigens. Using an extant dataset from a T cell profiling study, we tested whether HCMV proteins recognized by only a small minority of participants encompass any T cell epitopes. Our analyses demonstrate a prominent skewing of T cell responses away from most viral proteins—although they contain robust predicted CD8 T cell epitopes—in favor of a more restricted set of proteins. Our findings raise the possibility that HCMV may benefit from evading the T cell recognition of certain key proteins and that, contrary to current vaccine design approaches, including them as vaccine antigens could effectively take advantage of this vulnerability.
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spelling pubmed-106748792023-10-24 Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes Barry, Peter A. Iyer, Smita S. Gibson, Laura Vaccines (Basel) Article HCMV vaccine development has traditionally focused on viral antigens identified as key targets of neutralizing antibody (NAb) and/or T cell responses in healthy adults with chronic HCMV infection, such as glycoprotein B (gB), the glycoprotein H-anchored pentamer complex (PC), and the unique long 83 (UL83)-encoded phosphoprotein 65 (pp65). However, the protracted absence of a licensed HCMV vaccine that reduces the risk of infection in pregnancy regardless of serostatus warrants a systematic reassessment of assumptions informing vaccine design. To illustrate this imperative, we considered the hypothesis that HCMV proteins infrequently detected as targets of T cell responses may contain important vaccine antigens. Using an extant dataset from a T cell profiling study, we tested whether HCMV proteins recognized by only a small minority of participants encompass any T cell epitopes. Our analyses demonstrate a prominent skewing of T cell responses away from most viral proteins—although they contain robust predicted CD8 T cell epitopes—in favor of a more restricted set of proteins. Our findings raise the possibility that HCMV may benefit from evading the T cell recognition of certain key proteins and that, contrary to current vaccine design approaches, including them as vaccine antigens could effectively take advantage of this vulnerability. MDPI 2023-10-24 /pmc/articles/PMC10674879/ /pubmed/38005961 http://dx.doi.org/10.3390/vaccines11111629 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Barry, Peter A.
Iyer, Smita S.
Gibson, Laura
Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes
title Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes
title_full Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes
title_fullStr Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes
title_full_unstemmed Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes
title_short Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes
title_sort re-evaluating human cytomegalovirus vaccine design: prediction of t cell epitopes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674879/
https://www.ncbi.nlm.nih.gov/pubmed/38005961
http://dx.doi.org/10.3390/vaccines11111629
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