Recruitment of naive CD4+ T cells by the recombinant zoster vaccine correlates with persistent immunity
Kerry J. Laing, … , David M. Koelle, Adriana Weinberg
Kerry J. Laing, … , David M. Koelle, Adriana Weinberg
Published October 3, 2023
Citation Information: J Clin Invest. 2023;133(23):e172634. https://doi.org/10.1172/JCI172634.
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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 2

RZV expands gE-reactive CD4+ clonotypes mostly from naive and ZVL from memory CD4+ T cells.

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RZV expands gE-reactive CD4+ clonotypes mostly from naive and ZVL from m...
Data were derived from 10 RZV and 5 ZVL recipients. gE-reactive TRB identified at peak response (30 days after the single dose of ZVL or 30 days after the second dose of RZV) were matched to sorted naive and memory CD4+ T cells obtained before vaccination (Supplemental Figure 2). Memory indicates clonotypes exclusively matched to memory cells and naive includes all other clonotypes as described in the text. (A) Proportion of naive- and memory-matched peak and lasting clonotypes out of total peak clonotypes. Open circles represent results of individual RZV participants and closed circles of ZVL recipients with lines connecting paired results; P values for intergroup comparisons were calculated with Wilcoxon’s rank-sum test and for intragroup comparisons by Wilcoxon’s signed-rank pair test. (B) TRB clonotypes detected in sorted proliferated cells at peak only or both peak and 5-year (lasting) time points are enumerated as input and normalized to unique clonotypes per 1 × 106 stimulated PBMCs. These sequences were used to query for related TRB sequences using the TCRdist algorithm in search sets consisting of sorted memory and naive CD4+ T cell populations from prior to vaccination. The normalized number of clonotypes detected per 1 × 106 PBMCs with extended matching to TCRs detected at either peak or both time points (lasting) is indicated. Circles represent the normalized number per 1 × 106 input PBMCs of peak and lasting clonotypes detected with extended matching to have closely related TRB sequences in either memory or naive bulk sequencing repertoires and the ratio of naive to memory identification. P values calculated with Wilcoxon’s rank-sum test.