Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1785140932471947264 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10674879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT barrypetera reevaluatinghumancytomegalovirusvaccinedesignpredictionoftcellepitopes AT iyersmitas reevaluatinghumancytomegalovirusvaccinedesignpredictionoftcellepitopes AT gibsonlaura reevaluatinghumancytomegalovirusvaccinedesignpredictionoftcellepitopes |