Recruitment of naive CD4+ T cells by the recombinant zoster vaccine correlates with persistent immunity
Kerry J. Laing, Emily S. Ford, Michael J. Johnson, Myron J. Levin, David M. Koelle, Adriana Weinberg
Kerry J. Laing, Emily S. Ford, Michael J. Johnson, Myron J. Levin, David M. Koelle, Adriana Weinberg
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Research Article

Recruitment of naive CD4+ T cells by the recombinant zoster vaccine correlates with persistent immunity

Abstract

Herpes zoster (HZ) is a substantial problem for people with decreased cell-mediated immunity, including older adults. The first vaccine approved for HZ prevention, the zoster vaccine live (ZVL), which provided limited and short-lived protection, has been supplanted by the superior recombinant zoster vaccine (RZV), which provides robust and durable protection. To understand the mechanisms underlying the differential immunologic characteristics of the 2 vaccines, we used T cell receptor β chain sequencing and peptide–MHC class II tetramer staining to analyze recombinant glycoprotein E–specific (gE-specific) CD4+ T cell clonotypes in RZV and ZVL recipients. Compared with ZVL, RZV expanded more gE-specific CD4+ clonotypes, with greater breadth and higher frequency of public clonotypes. RZV recruited a higher proportion of clonotypes from naive than from memory cells, while ZVL recruited equally from memory and naive compartments. Compared with memory-derived, naive-derived clonotypes were more likely to last 5 or more years after immunization. Moreover, the frequency of tetramer+ persistent clones correlated with the frequency of tetramer+ naive CD4+ prevaccination T cells. We conclude that the ability of RZV to recruit naive CD4+ T cells into the response may contribute to the durability of its effect. The abundance, breadth, and frequency of public clonotypes may further add to its protective effect.

Authors

Kerry J. Laing, Emily S. Ford, Michael J. Johnson, Myron J. Levin, David M. Koelle, Adriana Weinberg

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Figure 1

gE-reactive CD4+ T cell clonotypes selected by ZVL or RZV administration.

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gE-reactive CD4+ T cell clonotypes selected by ZVL or RZV administration...
Data were derived from 5 ZVL and 10 RZV recipients. CD4+ T cells expanded in culture for 5 days in the presence of gE peptide pools (gating strategy in Supplemental Figure 1) were submitted for TRB sequencing. (A) Combined number of unique gE-reactive CD4+ T cell clonotypes, normalized by number of stimulated PBMCs, identified in individual ZVL or RZV participants 30 days after the single dose of ZVL or 30 days after the second dose of RZV (peak response) and/or 5 years after vaccination (persistent response). (B) Diversity of the clonotypes in A using the Chao1 analytical approach, which weights minor populations. (C) Distribution of the normalized number of unique gE-reactive clonotypes present at peak, persistent, or at both time points (lasting). (D) Diversity of the clonotypes in C. The horizontal lines indicate medians in each vaccine group. P values, calculated with Wilcoxon’s rank-sum tests, are shown on each graph.