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

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 [beta] chain sequencing and peptide-MHC class II tetramer staining to analyze recombinant glycoprotein E-specific (gE- specific) [CD4.sup.+] T cell clonotypes in RZV and ZVL recipients. Compared with ZVL, RZV expanded more gE-specific [CD4.sup.+] 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.sup.+] persistent clones correlated with the frequency of [tetramer.sup.+] naive [CD4.sup.+] prevaccination T cells. We conclude that the ability of RZV to recruit naive [CD4.sup.+] 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.
Introduction Herpes zoster (HZ) is a severe disease caused by reactivation of varicella-zoster virus (VZV) that is not optimally controlled by the immune system. Protection against HZ is primarily mediated [...]