title: 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.
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).
authors: Department of Pediatrics, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors: Jin Han
authors: http://orcid.org/0000-0003-1610-6742
authors: JH
authors: Kang
authors: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea. hoanlee@snu.ac.kr.
authors: Hoan Jong
authors: http://orcid.org/0000-0001-9643-3692
authors: HJ
authors: Lee
authors: Department of Pediatrics, Ewha Womans University Mokdong Hospital, Seoul, Korea.
authors: Kyung Hyo
authors: http://orcid.org/0000-0002-0333-6808
authors: KH
authors: Kim
authors: Department of Pediatrics, Hanyang University Medical Center, Seoul, Korea.
authors: Sung Hee
authors: http://orcid.org/0000-0001-6943-5430
authors: SH
authors: Oh
authors: Department of Pediatrics, Kyung Hee University Hospital, Seoul, Korea.
authors: Sung Ho
authors: http://orcid.org/0000-0003-0540-5747
authors: SH
authors: Cha
authors: Department of Pediatrics, KEPCO Medical Center, Seoul, Korea.
authors: Jin
authors: http://orcid.org/0000-0002-6039-2224
authors: J
authors: Lee
authors: Department of Pediatrics, Inje University Ilsan Paik Hospital, Ilsan, Korea.
authors: Nam Hee
authors: http://orcid.org/0000-0002-1793-1392
authors: NH
authors: Kim
authors: Department of Pediatrics, Eulji University School of Medicine, Eulji General Hospital, Seoul, Korea.
authors: Byung Wook
authors: http://orcid.org/0000-0003-3147-9061
authors: BW
authors: Eun
authors: Department of Pediatrics, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors: Chang Hwi
authors: http://orcid.org/0000-0001-5293-4428
authors: CH
authors: Kim
authors: Department of Pediatrics, Inha University Hospital, Incheon, Korea.
authors: Young Jin
authors: http://orcid.org/0000-0002-0878-9515
authors: YJ
authors: Hong
authors: Department of Pediatrics, The Catholic University of Korea, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea.
authors: Hyun Hee
authors: http://orcid.org/0000-0002-7196-2894
authors: HH
authors: Kim
authors: Department of Pediatrics, The Catholic University of Korea, Daejeon St. Mary's Hospital, Daejeon, Korea.
authors: Kyung Yil
authors: http://orcid.org/0000-0001-6510-1580
authors: KY
authors: Lee
authors: Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
authors: Yae Jean
authors: http://orcid.org/0000-0002-8367-3424
authors: YJ
authors: Kim
authors: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors: Eun Young
authors: http://orcid.org/0000-0002-2286-4593
authors: EY
authors: Cho
authors: Sanofi Pasteur, Seoul, Korea.
authors: Hee Soo
authors: http://orcid.org/0000-0003-3149-9361
authors: HS
authors: Kim
authors: Sanofi Pasteur, Lyon, France.
authors: Fabrice
authors: http://orcid.org/0000-0002-8990-5222
authors: F
authors: Guitton
authors: Sanofi Pasteur, Lyon, France.
authors: Esteban
authors: http://orcid.org/0000-0001-8417-606X
authors: E
authors: Ortiz
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D044466:Asian People; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018073:Haemophilus Vaccines / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D011054:Poliovirus Vaccine, Inactivated / Q000276:immunology*; D056910:Republic of Korea; D013745:Tetanus Toxoid / Q000276:immunology*; D017778:Vaccines, Combined / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D011054:Poliovirus Vaccine, Inactivated; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; C541234:diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine
keywords: Clinical Trial; DTaP-IPV Vaccine; Hib Vaccine; Immunogenicity; Infants; Safety