RESUMO
OBJECTIVES: To evaluate the safety and immunogenicity of ZOSTAVAX administered concomitantly with inactivated influenza vaccine or sequentially in adults aged 50 and older. DESIGN: Randomized, blinded, placebo-controlled study. SETTING: Thirteen U.S. and seven European study sites. PARTICIPANTS: Three hundred eighty-two concomitantly, 380 sequentially vaccinated subjects. INTERVENTION: The concomitant vaccination group received influenza vaccine and ZOSTAVAX at separate injection sites on Day 1 and placebo at Week 4. The nonconcomitant vaccination group received influenza vaccine and placebo at separate injection sites on Day 1 and ZOSTAVAX at Week 4. MEASUREMENTS: Primary safety endpoints: vaccine-related serious adverse experiences (AEs) within 28 days postvaccination (PV); and diary card-prompted local and systemic AEs. Primary immunogenicity endpoints: geometric mean titer (GMT) and geometric mean fold rise (GMFR) from baseline of varicella-zoster virus (VZV) antibody (Ab) at 4 weeks PV according to glycoprotein enzyme-linked immunosorbent assay (gpELISA) and GMT of influenza Ab for the three vaccine strains (2005-2006 influenza season) at 4 weeks PV according to hemagglutination inhibition assay. Secondary immunogenicity endpoint: influenza seroconversion rates (SCRs). RESULTS: No serious AEs related to ZOSTAVAX were observed during the study. VZV Ab GMTs 4 weeks PV for the concomitant and sequential groups were 554 and 597 gpELISA U/mL, respectively. The estimated VZV Ab GMT ratio was 0.9 (95% confidence interval (CI)=0.8-1.0), indicating noninferior (P<.001 for the null hypothesis of GMT ratio <0.67) responses. Estimated VZV Ab GMFR from baseline in the concomitant group was 2.1 (95% CI=2.0-2.3), indicating acceptable fold rise. Estimated GMT ratios (concomitant/sequential) for influenza strains A(H1N1), A(H3N2), and B were 0.9 (95% CI=0.8-1.1), 1.1 (95% CI=0.9-1.3), and 0.9 (95% CI=0.8-1.1), respectively, and SCRs were comparable across both groups, with more than 85% achieving titers of 1:40 or greater, meeting regulatory criteria. CONCLUSION: ZOSTAVAX and influenza vaccine given concomitantly are generally well tolerated in adults aged 50 and older. Ab responses were similar whether ZOSTAVAX and influenza vaccine were given concomitantly or sequentially.
