Two HLA-A*0201-restricted epitopes identified from herpes glycoprotein B are recognized exclusively by CD8+ T cells from asymptomatic individuals and protect against ocular herpes (P4517)

Abstract

Abstract Identification of human “asymptomatic” HSV-1 epitopes that induce CD8+ T cells would help in designing an immunotherapeutic vaccine against herpes. Here, the HSV-1 gB sequence was screened for potential HLA-A*0201 CD8+ T cell epitopes using a variety of algorithms. The ability of these epitopes to induce multi-functional CD8+ T cell responses was compared in 10 “symptomatic” vs. 10 “asymptomatic” individuals. Ten potential epitope peptides were tested for affinity to HLA-A*0201. gB441-449 and gB561-569 exhibited high affinity to, and significantly stabilized, HLA-A*0201 molecules on the surface of T2 cells. Peptide-specific CD8+ T cell proliferation (CFSE dilution) and CD107a/b cytotoxic degranulation against these two epitopes was found in all 10 “asymptomatic” individuals. Recognition by “asymptomatic” CD8+ T cells was validated for the two epitopes using HLA/peptide tetramers. Staining for IFN-γ, IL-2, and TNF-α revealed dual- and triple-positive CD8+ T cells, indicating that these gB peptide-specific CD8+ T cells were (poly)functional. The CD8+ T cell responses to these two epitopes were absent in “symptomatic” individuals. A lipopeptide/rAdv5 prime/boost mucosal vaccine using these asymptomatic CD8+ epitopes induced strong, long lasting CD8+ T-cell protective immunity against ocular herpes in susceptible HLA-A*0201 “humanized” transgenic mice. The HSV-gB-epitope repertoire for human CD8+ T cells is more restricted than previously suspected.