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Advances in understanding the mechanism of action of adult vaccines
Anthony L. Cunningham, … , Kerrie J. Sandgren, Naomi R. Truong
Anthony L. Cunningham, … , Kerrie J. Sandgren, Naomi R. Truong
Published December 1, 2023
Citation Information: J Clin Invest. 2023;133(23):e175378. https://doi.org/10.1172/JCI175378.
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Advances in understanding the mechanism of action of adult vaccines

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Abstract

The occurrence of herpes zoster (HZ) correlates with declining memory T cells that had responded to earlier infection with varicella-zoster virus (VZV). There are especially lower T cell responses to the single immunodominant VZV protein glycoprotein E (gE) in people over 50 years of age, although antibody responses to VZV persist. Therefore, a live attenuated zoster vaccine (ZVL) aimed at restoring T cell responses was developed. Surprisingly, a recombinant zoster vaccine (RZV) consisting of gE combined with the AS01B adjuvant system proved superior in efficacy and durability. In this issue of the JCI, Laing, Ford, and colleagues showed that both vaccines stimulated preimmunization naive CD4+ T cells, not just memory CD4+ T cells, to gE, and recruited these naive responses into the overall memory response. However, compared with ZVL, RZV stimulated this response to a much greater degree. These results will help guide development of more effective and durable vaccines for older individuals.

Authors

Anthony L. Cunningham, Kerrie J. Sandgren, Naomi R. Truong

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Figure 1

CD4+ T cells respond to gE following the RZV.

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CD4+ T cells respond to gE following the RZV.
(A) Before vaccination, in...
(A) Before vaccination, individuals possess low total CD4+ T cell responses to VZV and low or absent memory CD4+ T cell responses to gE. Immunization by RZV results in predominantly naive CD4+ T cell stimulation by RZV, incorporating them into the memory T cell pool and peaking at one month after the second dose of vaccine. The response declines but persists over five years and the CD4+ T cell response to gE lasts for at least ten years. (B) The T cell receptor β (TRB) chain has a hypervariable complementarity-determining region 3 (CDR3), which encompasses the junction of three regions known as the variable, diversity, and joining regions, and is responsible for recognizing the gE antigen. Laing, Ford, and colleagues used the TRB sequences, including the CDR3 hypervariable region, to determine the frequency of gE-specific CD4+ T cell clonotypes and assess how they changed with time (21). Adapted from Migalska et al. (27).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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