Long-Term Immunological Persistence Of The Adjuvanted Recombinant Zoster Vaccine: Clinical Data And Mathematical Modeling

Abstract Background The adjuvanted recombinant zoster vaccine (RZV, GSK), administered to adults ≥ 50 years of age (YOA) demonstrated ≥ 90% efficacy against herpes zoster across all age cohorts. Vaccine-specific immune responses elicited by two RZV doses in adults ≥ 60 YOA have been shown to persist above pre-vaccination levels at least up to 9 years after initial vaccination. Here we present persistence of the humoral and cellular immunity and safety up to 10 years after initial vaccination as well as data from mathematical modeling, performed to predict immune persistence up to 15 years. Methods This phase IIIB, open-label extension trial (NCT02735915) included 70 participants who had received two RZV doses in the initial trial (NCT00434577) and builds on a previous extension trial (NCT01295320). Cellular and humoral immune responses up to year 10 after an initial 2-dose vaccination schedule are presented here. Additionally, prediction of immunological persistence at year 15 was assessed by mathematical modeling (Piecewise, Power-law, Fraser), using the individual subject values for available data up to year 10. Results The median frequency of varicella-zoster virus glycoprotein E (gE)-specific CD4+ T-cells expressing ≥ 2 activation markers plateaued at 3.3-fold above pre-vaccination levels starting around year 4 up to year 10 post-initial vaccination. Anti-gE antibody concentrations plateaued starting around year 3 up to year 10 post-initial vaccination.Ten years after initial vaccination, humoral responses remained 5.9-fold higher as compared with pre-initial vaccination levels (Figure 1). No relevant safety events were identified during the study (year 9–10 post-initial vaccination). In line with previous modeling data, the year 10 analysis predicts that both cellular and humoral immune responses will remain above pre-vaccination levels for at least 15 years after initial vaccination (Figures 2 and 3). Conclusion In adults vaccinated when ≥ 60 YOA, humoral and cellular immune responses induced by two RZV doses persist above pre-vaccination levels for at least 10 years post-initial vaccination. Mathematical modeling predicts a maintained vaccine-related immune response for at least 15 years after initial vaccination. Funding. GlaxoSmithKline Biologicals SA. Disclosures All Authors: No reported Disclosures.