Zoster Vaccination Increases the Breadth of CD4+ T Cells Responsive to Varicella Zoster Virus
KJ Laing, RM Russell, L Dong… - The Journal of …, 2015 - academic.oup.com
The Journal of infectious diseases, 2015•academic.oup.com
Background. The live, attenuated varicella vaccine strain (vOka) is the only licensed
therapeutic vaccine. Boost of varicella zoster virus (VZV)–specific cellular immunity is a likely
mechanism of action. We examined memory CD4+ T-cell responses to each VZV protein at
baseline and after zoster vaccination. Methods. Serial blood samples were collected from 12
subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-
cell and antibody assays. CD4+ T-cell lines enriched for VZV specificity were generated and …
therapeutic vaccine. Boost of varicella zoster virus (VZV)–specific cellular immunity is a likely
mechanism of action. We examined memory CD4+ T-cell responses to each VZV protein at
baseline and after zoster vaccination. Methods. Serial blood samples were collected from 12
subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-
cell and antibody assays. CD4+ T-cell lines enriched for VZV specificity were generated and …
Abstract
Background. The live, attenuated varicella vaccine strain (vOka) is the only licensed therapeutic vaccine. Boost of varicella zoster virus (VZV)–specific cellular immunity is a likely mechanism of action. We examined memory CD4+ T-cell responses to each VZV protein at baseline and after zoster vaccination.
Methods. Serial blood samples were collected from 12 subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-cell and antibody assays. CD4+ T-cell lines enriched for VZV specificity were generated and probed for proliferative responses to every VZV protein and selected peptide sets.
Results. Zoster vaccination increased the median magnitude (2.3-fold) and breadth (4.2-fold) of VZV-specific CD4+ T cells one month post-vaccination. Both measures declined by 6 months. The most prevalent responses at baseline included VZV open reading frames (ORFs) 68, 4, 37, and 63. After vaccination, responses to ORFs 40, 67, 9, 59, 12, 62, and 18 were also prevalent. The immunogenicity of ORF9 and ORF18 were confirmed using peptides, defining a large number of discrete CD4 T-cell epitopes.
Conclusions. The breadth and magnitude of the VZV-specific CD4+ T-cell response increase after zoster vaccination. In addition to glycoprotein E (ORF68), we identified antigenic ORFs that may be useful components of subunit vaccines.
Oxford University Press