Concomitant administration of hepatitis A vaccine with measles/mumps/rubella/varicella and pneumococcal vaccines in healthy 12- to 23-month-old children

Abstract

This open-label, multicenter, randomized, comparative study evaluated immunogenicity, safety and tolerability of concomitant (Group 1; n = 330) vs. non-concomitant (Group 2; n = 323) VAQTA™ (25U/0.5 mL) (hepatitis A vaccine; HAV) with ProQuad™ (measles/mumps/rubella/varicella; MMRV) and Prevnar™ (7-valent pneumococcal; PCV-7) in healthy, 12–23 mo old children. Group 1 received HAV/MMRV/PCV-7 concomitantly on Day 1 and second doses of HAV/MMRV at Week 24. Group 2 received MMRV/PCV-7 on Day 1, HAV at Weeks 6 and 30 and MMRV at Week 34. Hepatitis A seropositivity rate (SPR: ≥10 mIU/mL; 4 weeks postdose 2), varicella zoster-virus (VZV) SPR (≥5 gpELISA units/mL) and geometric mean titers (GMT) to S. pneumoniae were examined. Injection-site and systemic adverse experiences (AEs) and daily temperatures were collected. Hepatitis A SPR were 100% for Group 1 and 99.4% for Group 2 after two HAV doses; risk difference = 0.7 (95%CI: −1.4,3.8, non-inferior) regardless of initial serostatus. VZV SPR was 93.3% for Group 1 and 98.3% for Group 2; risk difference = −5.1 (95%CI: −9.3,−1.4; non-inferior). S. pneumoniae GMT fold-difference (7 serotypes) ranged from 0.9 to 1.1; non-inferior. No statistically significant differences in the incidence of individual AEs were seen when HAV was administered concomitantly vs. non-concomitantly. Three (all Group 2 post-administration of MMRV/PCV-7) of 11 serious AEs were considered possibly vaccine-related: dehydration and gastroenteritis (same subject) on Day 52; febrile seizure on Day 9. No deaths were reported. Antibody responses to each vaccine given concomitantly were non-inferior to HAV given non-concomitantly with MMRV and PCV-7. Administration of HAV with PCV-7 and MMRV had an acceptable safety profile in 12- to 23-mo-old children.

Keywords: :

• safety
• immunogenicity
• hepatitis A
• measles
• mumps
• rubella
• varicella
• pneumococcal
• vaccine
• concomitant use

Disclosure of Potential Conflicts of Interest

Other than employees of Merck Sharp and Dohme Corp. (as indicated on the title page), all authors have been investigators for the sponsor. Employees may hold stock and/or stock options in the company.

This study was funded by Merck Sharp and Dohme Corp. (sponsor). In conjunction with the external investigators, this study was designed, executed, and analyzed by the sponsor. The sponsor formally reviewed a penultimate draft. All co-authors approved the final version of the manuscript.

Acknowledgments

The authors would like to thank all the subjects who participated in this study. VAQTA^® Protocol 067 Study Group: WP Andrews (GA), E Barranco (PR), MJ Benbow (TX), HH Bernstein (NH), HR Bertrand (SC), CC Chang (CA), T Crum (WA), AL Duke (AR), ER Franklin (NC), IP Godoy (CA), E Goldblatt (AL), U Goswami (IL), SE Grogg (OK), E Hammel (CA), B Harvey (AR), CD Jackson (AR), NB Klein (CA), W Johnston (AL), J Kratzer (CA), KH Lee (CA), E Maddela (CA), LK Nassri (AR), A Naz (CA), CD Nelms (TX), LO Sass (VA), TJ Schechtman (FL), SD Senders (OH), OS Shaikh (OH), JS Shepard (OH), PE Silas (UT), M Sperling (CA), RA Stanford (AR), BJ Sullivan (WI), RJ Yetman (TX).

Study identification: V251–067

CLINICALTRIALS.GOV identifier: NCT00312858

Data from this manuscript were presented in poster format at the 2011 European Society for Paediatric Infectious Diseases (abstract #371).

Yetman, Shepard, Duke, Shaikh: enrollment of subjects and/or data collection, analysis and interpretation of data and preparation of manuscript. Stek, Petrecz: analysis and interpretation of data and preparation of manuscript. Klopfer, Kuter, Schödel, Lee: study concept and design, analysis and interpretation of data and preparation of manuscript.