Barry, Peter AIyer, Smita SGibson, Laura2025-07-312025-07-312023-10-24Barry PA, Iyer SS, Gibson L. Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes. Vaccines (Basel). 2023 Oct 24;11(11):1629. doi: 10.3390/vaccines11111629. PMID: 38005961; PMCID: PMC10674879.2076-393X10.3390/vaccines1111162938005961vaccines11111629https://hdl.handle.net/20.500.14038/54660HCMV 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 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.enCopyright: © 2023 by the authors. 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/).http://creativecommons.org/licenses/by/4.0/bioinformaticscytomegalovirusunconventional T cell antigen candidatesvaccineJournal Article