A comparison of the immunogenicity of a live attenuated herpes zoster vaccine (ZV) and the recombinant gE/AS01B candidate vaccine in older adults

Abstract

Abstract Herpes zoster (HZ) has high morbidity in older adults. ZV, which is recommended for individuals ≥60 y, is 51% effective against HZ in the 1st 3 y after vaccination; efficacy decreases with the age of the vaccinee; and wanes to ~40% at 5 y. gE/ASO1B is a recombinant adjuvanted vaccine with 97% efficacy against HZ that does not vary with age of the vaccinee and wanes to 87% at 4y. We compared the cell-mediated immunity (CMI) of ZV and gE/ASO1B at 30 d after the last dose of vaccine and at 1 y. Subjects were 50–70+ yoa who never received ZV (1ary) and adults ≥70 yoa who received ZV ≥5 y previously (boosted). Participants received ZV at entry or gE/ASO1B at 0 and 60 d. Blood from days 0, 30 (ZV peak response), 90 (peak gE/ASO1B) and 365 was used to measure CMI to varicella zoster virus (VZV) and to gE by IFNg and IL2 fluorospot [spot forming cells/106 PBMC (SFC)] and by flow cytometry assessing VZV- and gE-specific proliferation and effector (Teff), effector memory (Tem), and central memory (Tcm) outcomes. The higher CMI responses that best distinguished gE/ASO1B from ZV recipients after adjusting for age, gender, prior ZV administration and baseline CMI were: 1) VZV-specific IL2 and gE-specific IL2 and IFNg SFC at peak response (p≤0.004); 2) higher VZV-specific CD8+ and gE-specific CD4+ and CD8+ responses measured by proliferation at peak (p<0.05); 3) higher CD4+ Tcm% and Tem% and lower Teff% at peak response (p≤0.005); 4) higher VZV-specific and gE-specific IL2 and IFNg SFC at 1 y in all gE/ASO1B groups, but only in the boosted ZV group. CMI did not differ among gE/ASO1B recipients by age or prior ZV administration. The higher memory CD4+ and CD8+ responses detected in gE/AS01B recipients might contribute to its superior efficacy and persistence of protection against HZ.