The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants

Jin Han Kang, Hoan Jong Lee, Kyung Hyo Kim, Sung Hee Oh, Sung Ho Cha, Jin Lee, Nam Hee Kim, Byung Wook Eun, Chang Hwi Kim, Young Jin Hong, Hyun Hee Kim, Kyung Yil Lee, Yae Jean Kim, Eun Young Cho, Hee Soo Kim, Fabrice Guitton, Esteban Ortiz, Jin Han Kang, Hoan Jong Lee, Kyung Hyo Kim, Sung Hee Oh, Sung Ho Cha, Jin Lee, Nam Hee Kim, Byung Wook Eun, Chang Hwi Kim, Young Jin Hong, Hyun Hee Kim, Kyung Yil Lee, Yae Jean Kim, Eun Young Cho, Hee Soo Kim, Fabrice Guitton, Esteban Ortiz

Abstract

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 μg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 μg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

Keywords: Clinical Trial; DTaP-IPV Vaccine; Hib Vaccine; Immunogenicity; Infants; Safety.

Conflict of interest statement

DISCLOSURE: Hee Soo Kim, Fabrice Guitton, and Esteban Ortiz are full-time salaried, employees of the study sponsor. Other authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Subject disposition flow chart – safety set.
Fig. 2
Fig. 2
Proportions of the two study groups achieving the respective protective antibody cut-offs, or a seroresponse for the pertussis antigens, at month 7 (with 95% CI). CI, confidence interval; DTaP-IPV, diphtheria-tetanus-acellular pertussis-inactivated polio; PRP, polyribosyl ribitol phosphate; PT, pertussis toxin; FHA, filamentous hemagglutinin.
Fig. 3
Fig. 3
Proportions of each study group (95% CI bars) reporting solicited local and systemic reactions in the two study groups after each dose. Local reactions are shown for each vaccination site (DTaP-IPV, Hib, and DTaP-IPV//Hib).

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