Immunogenicity and safety of the diphtheria, pertussis, tetanus and inactivated poliovirus vaccine when co-administered with the human rotavirus vaccine (Rotarix) in healthy Japanese infants: a phase IV randomized study

Paul Gillard,Tsuyoshi Tamura,Haruo Kuroki,Yoshiyuki Morikawa,Leentje Moerman,Jose Parra,Yurina Kitamura,Kazuko Mihara,Arisa Okamasa

doi:10.1080/21645515.2018.1564441

Abstract

ABSTRACT Rotavirus infections have been reported to account for 40–50% of all hospitalized acute gastroenteritis cases in young children (<5 years) in Japan. Since 2011, Rotarix containing the live attenuated human rotavirus RIX4414 strain (HRV) has been licensed in Japan for infants. Vaccination against rotavirus is optional in Japan whereas administration of diphtheria, pertussis, tetanus, and inactivated poliovirus (DPT-IPV) vaccine is part of the national routine immunization program. In this open-label, randomized, controlled, multicenter study, we evaluated the immunogenicity and safety of the DPT-IPV vaccine (Squarekids) administered concomitantly or staggered with the liquid HRV (Rotarix) vaccine in healthy Japanese infants. A total of 292 infants aged 6–12 weeks were randomly assigned to receive DPT-IPV vaccine and HRV vaccine co-administered (n = 147) or staggered (n = 145). Immune responses to DPT-IPV vaccine were evaluated by measuring the post-vaccination serum antibody titers/concentrations to each antigen at one month following the third dose of DPT-IPV vaccine. Seroprotection/seropositivity against each of the diphtheria, pertussis (pertussis toxin and filamentous hemagglutinin), tetanus, and poliovirus type 1, 2 and 3 antigens was 92.8% or higher in both groups. In terms of immunogenicity, DPT-IPV vaccine co-administered with HRV vaccine was shown to be non-inferior to DPT-IPV vaccine with a staggered administration. The safety profile was comparable in the two vaccine groups with no vaccine-related serious adverse events, no deaths and no cases of intussusception. These results support co-administration of HRV vaccine with DPT-IPV vaccine in Japan. ClinicalTrials.gov NCT02907216

Highlights

By the age of 5 years, nearly every child worldwide will have suffered one or more rotavirus gastroenteritis (RVGE) episodes
The first dose of the human rotavirus (HRV) vaccine is recommended to be administered during the age interval 6–14 weeks with a schedule of 2 vaccinations with HRV vaccine, or 3 vaccinations with human-bovine reassortant rotavirus (HBRV) vaccine
Since the routine vaccination program requires that children receive several vaccines around the same age, it is important to investigate whether concomitant administration of these 2 vaccines, DPT-IPV vaccine and HRV vaccine, could lead to interactions with regard to immunogenicity, safety and reactogenicity

Summary

Introduction

By the age of 5 years, nearly every child worldwide will have suffered one or more rotavirus gastroenteritis (RVGE) episodes. In Japan, a substantial disease burden of hospitalizations for acute gastroenteritis (AGE) of children younger than 5 years has been observed, with annual incidence rates up to 17.6 per 1,000 children.[5] Rotavirus infections accounted for 40–50% of all hospitalizations for AGE.[6,7]. The WHO considers rotavirus vaccination as an effective measure to prevent RVGE and recommends it to be done as soon as possible from 6 weeks of age, if possible along with the diphtheriapertussis-tetanus (DPT) vaccination to ensure induction of protection prior to the peak incidence of natural rotavirus infection.[2] Rotavirus vaccines are recommended to be part of all national immunization programs, in countries with high RVGE-associated fatality rates.[2] A study from Mexico conducted 2 to 3 years after the introduction of rotavirus vaccine showed a 35% reduction in diarrhea-related deaths in children

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