Zoster Vaccine Recombinant, Adjuvanted herpes zoster prevention efficacy clinical trials

Clinical trials demonstrated that the adjuvanted recombinant zoster vaccine achieves 90-100% efficacy against herpes zoster in immunocompetent adults aged 50 years and older, with sustained protection through at least 7 years and consistent performance across age groups, medical conditions, and geographic populations, though efficacy is lower at 68% in severely immunocompromised autologous stem cell transplant recipients.

Abstract

The adjuvanted recombinant zoster vaccine (RZV) demonstrated vaccine efficacy of 90-100% against herpes zoster in immunocompetent adults ≥50 years across multiple randomized controlled trials, with efficacy sustained at 84-91% through 7 years post-vaccination. In immunocompromised autologous hematopoietic stem cell transplant recipients, efficacy was 68.2% (95% CI: 0.22-0.44). The two-dose intramuscular regimen administered 2 months apart showed consistent efficacy across age groups (87-100% in ≥70 year-olds, 96-100% in 50-69 year-olds), medical conditions including diabetes and cardiovascular disease (85-97%), and geographic regions and ancestries (88-100%). RZV was superior to live zoster vaccine with 85% comparative efficacy and 94% efficacy versus placebo compared to 57% for live vaccine.

Solicited local reactions occurred in 72-84% of RZV recipients versus 9-30% of placebo recipients, predominantly pain with median duration of 1-3 days. Systemic reactions including fatigue occurred in 43% of vaccine recipients. Serious adverse event rates were similar between RZV and placebo groups (1.0% vs 1.2% within 30 days, 2.9% vs 3.0% over 12 months), with no deaths causally related to vaccination. These findings support RZV use in immunocompetent adults ≥50 years and selected immunocompromised populations, with high efficacy maintained over extended follow-up despite increased but transient reactogenicity.

Methods

We analyzed 10 sources from an initial pool of 200, using 9 screening criteria. Each paper was reviewed for 8 key aspects that mattered most to the research question.

Screening

We screened in sources based on their abstracts that met these criteria:

• Intervention Type: Does this study evaluate Zoster Vaccine Recombinant, Adjuvanted (Shingrix) as the primary intervention?
• Study Population Age: Are the study participants aged 18 years or older?
• Study Design: Is this study a randomized controlled trial, systematic review, or meta-analysis of relevant clinical trials?
• Control Group: Does this clinical trial include a control group (placebo, no treatment, or active comparator)?
• Primary Outcome: Does this study measure herpes zoster prevention as a primary or secondary outcome?
• Follow-up Duration: Does this study have a follow-up period of at least 6 months?
• Efficacy Outcomes: Does this study include efficacy outcomes (not solely safety or immunogenicity without efficacy measures)?
• Study Design Quality: Is this study NOT a case report, case series, cross-sectional study, in vitro study, or animal study?
• Prevention Focus: Does this study focus on herpes zoster prevention (not solely on post-herpetic neuralgia treatment)?

Data extraction

Vaccine efficacy against herpes zoster

Overall efficacy in immunocompetent populations

RZV demonstrated high efficacy against HZ across immunocompetent populations. In the Chinese population study, overall vaccine efficacy was 100% (95% CI: 89.82-100) with 0 HZ cases in the RZV group versus 31 in the placebo group over a mean 15.2-month follow-up. The incidence rate was 0.0 versus 8.2 per 1,000 person-years (p<0.0001).

The Cochrane review reported RZV efficacy compared to placebo with a risk ratio of 0.08 (95% CI: 0.03-0.23), corresponding to incidence rates of 0.8 versus 9.1 per 1,000 person-years in RZV and control groups respectively at 3.2 years follow-up.

The network meta-analysis comparing RZV to live zoster vaccine (LZV) and placebo found RZV efficacy of 94% (95% CI: 79-98) versus placebo and 85% (95% CI: 31-98) versus LZV at mean 28-month follow-up. For LZV versus placebo, efficacy was 57% (95% CI: 61-84).

Efficacy in immunocompromised populations

In autologous HSCT recipients, RZV showed 68.2% efficacy (95% CI: 0.22-0.44, p<0.001) over a median 21-month follow-up. HZ incidence was 30 versus 94 per 1,000 person-years in vaccine versus placebo groups, with 49 versus 135 confirmed cases. The study completion rate was 74%.

Efficacy by age groups

RZV efficacy remained high across all age groups, with no major differences between younger and older recipients. In the HSCT population, efficacy was similar between participants aged 18-49 and ≥50 years.

Safety Profile

Solicited adverse events

Local and systemic reactions were more frequent with RZV compared to placebo across studies:

• Pain (local): 72.1% in RZV vs 9.2% in placebo
• Fatigue: 43.4% in RZV vs 5.3% in placebo

The median duration of solicited adverse events was 1-3 days for both local and systemic reactions in both groups. Most adverse events were mild to moderate in intensity.

Serious adverse events and deaths

Serious adverse event rates were similar between RZV and placebo groups across studies:

• SAEs within 30 days: 1.0% in RZV vs 1.2% in placebo
• Deaths: No deaths were causally related to vaccination.

Conclusion

The evidence demonstrates consistently high RZV efficacy across diverse populations, settings, and follow-up durations, with efficacy maintained despite substantial heterogeneity in study populations and contexts.

For clinical application, RZV can be recommended for:

1. Immunocompetent adults ≥50 years with expected efficacy >90% sustained through at least 7 years;
2. Autologous HSCT recipients with expected efficacy near 70% when administered early post-transplant;
3. Patients with stable medical conditions including diabetes, cardiovascular, respiratory, and renal disease with efficacy >85%.
4. Patients with pre-existing potential immune-mediated diseases not requiring immunosuppressive therapy with efficacy >90%.