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Identification of protective T-cell antigens for smallpox vaccines
#MMPMID32747299
Ando J
; Ngo MC
; Ando M
; Leen A
; Rooney CM
Cytotherapy
2020[Nov]; 22
(11
): 642-652
PMID32747299
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BACKGROUND AIMS: E3L is an immediate-early protein of vaccinia virus (VV) that is
detected within 0.5 h of infection, potentially before the many immune evasion
genes of vaccinia can exert their protective effects. E3L is highly conserved
among orthopoxviruses and hence could provide important protective T-cell
epitopes that should be retained in any subunit or attenuated vaccine. We have
therefore evaluated the immunogenicity of E3L in healthy VV-vaccinated donors.
METHODS: Peripheral blood mononuclear cells from healthy volunteers (n = 13) who
had previously received a smallpox vaccine (Dryvax) were activated and expanded
using overlapping E3L peptides and their function, specificity and antiviral
activity was analyzed. E3L-specific T cells were expanded from 7 of 12 (58.3%)
vaccinated healthy donors. Twenty-five percent of these produced CD8+ T-cell
responses and 87.5% produced CD4+ T cells. We identified epitopes restricted by
HLA-B35 and HLA-DR15. RESULTS: E3L-specific T cells killed peptide-loaded target
cells as well as vaccinia-infected cells, but only CD8+ T cells could prevent the
spread of infectious virus in virus inhibition assays. The epitopes recognized by
E3L-specific T cells were shared with monkeypox, and although there was a single
amino acid change in the variola epitope homolog, it was recognized by
vaccinia-specific T-cells. CONCLUSIONS: It might be important to include E3L in
any deletion mutant or subunit vaccine and E3L could provide a useful antigen to
monitor protective immunity in humans.
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