Immunogenicity and safety of a combined DTPa-IPV/Hib vaccine administered as a three-dose primary vaccination course in healthy Korean infants: phase III, randomized study

Ki Hwan Kim, Chun Soo Kim, Hwang Min Kim, Jong-Duck Kim, Sang Hyuk Ma, Dong Ho Kim, Pyoung-Han Hwang, Ji-Whan Han, Taek-Jin Lee, Joon Hyung Kim, Naveen Karkada, Narcisa Mesaros, Woo-Yun Sohn, Jong-Hyun Kim, Ki Hwan Kim, Chun Soo Kim, Hwang Min Kim, Jong-Duck Kim, Sang Hyuk Ma, Dong Ho Kim, Pyoung-Han Hwang, Ji-Whan Han, Taek-Jin Lee, Joon Hyung Kim, Naveen Karkada, Narcisa Mesaros, Woo-Yun Sohn, Jong-Hyun Kim

Abstract

We assessed the immunogenicity and safety of a three-dose primary vaccination schedule with the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Korean infants. In this phase III open-label, multicenter study (NCT01309646), healthy infants aged 42-69 days (randomized 1:1) received three doses of either pentavalent DTPa-IPV/Hib (DTPa-IPV/Hib group) or DTPa-IPV and Hib vaccines administered separately (DTPa-IPV+Hib group) at 2, 4, 6 months of age. The primary objective was to demonstrate non-inferiority of DTPa-IPV/Hib compared to DTPa-IPV+Hib vaccines in terms of immune responses to all vaccine antigens, 1 month post-dose 3. Solicited symptoms (local and general) were recorded during 4 days, and unsolicited adverse events (AEs) during 31 days, after each vaccination. Serious AEs (SAEs) were recorded throughout the study duration. The immunogenicity of the pentavalent DTPa-IPV/Hib vaccine was non-inferior compared to concomitant administration of DTPa-IPV+Hib vaccines. One month post-dose 3, nearly all infants had antibody levels above the seroprotective thresholds for anti-diphtheria toxoid, anti-tetanus toxoid, anti-polyribosyl-ribitol phosphate, and anti-poliovirus type 1, 2 and 3, and had antibody levels above the seropositive thresholds for anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies. A vaccine response for PT, FHA and PRN was observed in at least 96.7% of study participants. Anti-PRP geometric mean concentrations appeared lower for the DTPa-IPV/Hib group (8.456 µg/mL) than for the DTPa-IPV+Hib group (18.700 µg/mL). In both groups, the most common solicited symptoms were injection site redness and irritability. Fifty-seven SAEs were reported throughout the study; none were considered to be vaccination related.

Keywords: type b; DTPa-IPV/Hib; acellular pertussis; diphtheria; immunogenicity; infants; poliovirus; reactogenicity; safety; tetanus.

Figures

Figure 1.
Figure 1.
Participant flow diagram. N, number of participants in each group; TVC, total vaccinated cohort; ATP, according-to-protocol. Infants in DTPa-IPV/Hib group received 3 doses of combined diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis and Haemophilus influenzae type b vaccine at 2, 4, 6 months of age and infants in DTPa-IPV+ Hib group received 3 concomitant doses of diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine and Haemophilus influenzae type b vaccine at 2, 4, 6 months of age.
Figure 2.
Figure 2.
Incidence of solicited local and general symptoms reported up to 4 days post-vaccination (total vaccinated cohort). Infants in DTPa-IPV/Hib group received 3 doses of combined diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis and Haemophilus influenzae type b vaccine at 2, 4, 6 months of age and infants in DTPa-IPV+ Hib group received 3 concomitant doses of diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine and Haemophilus influenzae type b vaccine at 2, 4, 6 months of age. The results are reported overall/dose. The error bars indicate 95% confidence intervals. Grade 3 were defined as adverse events preventing normal activity, pain upon limb movement or a spontaneously painful limb, redness and swelling >20 mm in diameter, a tympanic temperature >39.0°C, loss of appetite resulting in not eating at all, drowsiness that prevented normal activity, and irritability/fussiness resulting in crying that cannot be comforted.

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