Recombinant zoster vaccine may be effective in older adults, including the immunocompromised

1. In this analysis of target trial emulations, at least one dose of the recombinant zoster vaccine was effective in older adults, including immunocompromised adults.

2. Administration of a second dose of the vaccine was found to confer additional effectiveness against any herpes zoster outcome.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The adjuvanted two-dose recombinant zoster vaccine (RZV) alleviated limitations of previous live zoster vaccines, including waning immunity over time and inability to use in immunocompromised individuals. Although the RZV is theoretically safe in immunocompromised adults, this population has been excluded from the major trials of the vaccine to date. Further, considering that the two-dose schedule could be disrupted by access-related factors, there is limited evidence regarding the benefit of a single dose. This study aimed to determine the effectiveness of RZV and the additional benefit of two RZV doses compared with one 1 dose in older adults. After pooling the results of twelve emulated trials, it was found that at least 1 RZV dose provided a vaccine effectiveness (VE) of over fifty percent against any herpes zoster (HZ) outcome, as well as specifically against HZ ophthalmicus (HZO). Further, one dose had an effectiveness of nearly three-quarters against post-herpetic neuralgia (PHN). A similar VE against any HZ outcome was seen between immunocompromised and immunocompetent individuals. Black individuals had a much lower VE against any HZ outcome, although this estimate was imprecise due to the low percentage of Black participants in the study. In a second analysis, receipt of a second RZV dose provided significant additional VE against any HZ outcome compared with one dose. The generalizability of this study is limited by an inability to estimate VE among 50- to 64-year-olds, a short study period, and an inability to assess the safety of RZV. Regardless, these results suggest that RZV is effective in older adults, including immunocompromised adults, with two doses of RZV conferring further benefits than one.

Click to read this study in AIM

Relevant Reading: Recombinant zoster vaccine in immunocompetent and immunocompromised adults: A review of clinical studies

In-Depth [randomized controlled trial]: This analysis of pooled target trial emulations aimed to assess the effectiveness of RZV and the additional benefit of 2 RZV doses compared with 1 dose in older adults. Patient data were obtained from a 20% random sample of adults aged 65 years or older enrolled in Medicare Parts A, B, and D. Patients were eligible for analysis 1 if they were aged 65 years or older and had no prior claims for HZ or RZV vaccination. Patients were eligible for analysis 2 if they were eligible for analysis 1 and had received at least 1 dose of RZV during a later timepoint. The primary outcome for both analyses was any HZ-related outcome, and secondary outcomes included HZO and PHN. In analysis 1, a total of 36,762,933 observations were seen among 3,456,555 unique individuals. The overall 1-year VE of at least 1 RZV dose was 56.1% (95% CI, 53.1% to 59.0%) against any HZ outcome, 55.2% (95% CI, 43.5% to 64.5%) against HZO, and 72.0% (95% CI, 63.7% to 78.4%) against PHN. Vaccination avoided an estimated 698 HZ cases, 58 HZO cases, and 78 PHN cases per 100,000 people. Black individuals had a relatively low VE of 18.2% (95% CI, 0.00% to 49.1%), although this estimate was imprecise due to a low percentage of Black participants in the trials. Immunocompromised individuals had a similar VE (54.2% [95% CI, 44.7% to 62.1%]) compared with that of immunocompetent individuals (56.5% [CI, 53.2% to 59.5%]). In analysis 2, a total of 386,802 observations were seen among 146,296 unique individuals across all trials. The 1-dose and 2-dose groups had similar distributions of demographic characteristics including race, sex, and age. The median length of time between the first and second doses among the 2-dose group was 136 days. Receiving 2 RZV doses conferred a relative VE of 67.9% (95% CI, 64.2% to 71.3%) against any HZ outcome, a relative VE of 67.4% (95% CI, 52.0% to 77.8%) for HZO, and a relative VE of 80.7% (95% CI, 67.3% to 88.6%) for PHN compared with one dose. A sensitivity analysis in which the second dose was given 2 to 6 months after the first dose showed a similar relative VE of 68.1% (95% CI, 64.3% to 71.5%). Overall, this study suggests that at least 1 dose of RZV is effective in older adults, and that a second dose confers additional benefit.

Image: PD

©2025 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.