Journal of Vaccines & Vaccination

Abstract

Immunogenicity and Safety of an Inactivated Hepatitis A Vaccine Given with Measles-Mumps-Rubella Vaccine to 12-13 Month Old Turkish Children

Kadriye YURDAKÖK, Mustafa BAKIR, Tolga İNCE, Songül YALÇIN, Elif ÖZMERT, Ahmet SOYSAL, Tamer PEHLIVAN and Anvar RASULI

Background: The epidemiology of hepatitis A in Turkey favor routine vaccination of children. This study assessed compatibility of a monovalent hepatitis A vaccine with the measles-mumps-rubella (MMR) combination vaccine used in the national immunization calendar at 12-15 months of age. Methods: Hepatitis A seronegative participants were randomized equally to hepatitis A vaccine followed by MMR vaccine 28 days later (Group A), MMR vaccine followed by hepatitis A vaccine 28 days later (Group B), or one dose each of hepatitis A and MMR vaccines given on Day 0 (Group C). All participants received a hepatitis A booster dose 6 months later. Results: A total of 470 seronegative (anti-hepatitis A concentration ≥20 mIU/mL) participants were randomized: 188 to Group A, 94 to Group B and 188 to Group C. The hepatitis A seroprotection rates (≥20 mIU/mL), 1 month after the first vaccination were 93.6% (Group A) and 92.7% (Group C) by a microparticle enzyme immunoassay (MEIA). Using a more sensitive electrochemiluminescence immunoassay (ECLIA), the corresponding seropositivity rates were 100 and 99.4%. Non-inferiority of seroprotection against hepatitis A was demonstrated for concomitant versus non-concomitant vaccination using ECLIA, but not MEIA. After booster, all participants had anti-hepatitis titers ≥20 mIU/mL and anti-hepatitis geometric mean concentrations of 5,078 mIU/mL (Group A), 3,271 mIU/mL (Group B) and 4,314 mIU/mL (Group C). Following primary vaccination, measles (≥120 mIU/mL) and mumps (≥ 10 AU/mL) seroprotection rates were 96.5% with both separate and concomitant vaccination. The rubella seroprotection (≥ 10 AU/mL) rates were 97.6 and 96.7% following separate and concomitant vaccination, respectively. Reactogenicity increased slightly with concomitant administration; both vaccines were well tolerated. Conclusions: The immune response to the hepatitis A vaccine was not impaired by concomitant administration with MMR vaccine. Non-inferiority of seroprotection was demonstrated with the more sensitive of two assays used to evaluate anti-hepatitis A antibody.