Safety and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa-HBV-IPV/Hib in Vietnamese infants

Abstract

Background: Pneumococcal infections are a major cause of infant mortality/morbidity in developing countries. This study assessed the safety and reactogenicity of PHiD-CV (Synflorix™; GlaxoSmithKline Biologicals) co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa™; GlaxoSmithKline Biologicals) to infants in Vietnam, a developing country setting. Methods: In this phase III, single centre, open-label study (NCT01153841), infants were randomised (2:1) to receive 3-dose primary vaccination at 2, 3 and 4 months of age with either PHiD-CV co-administered with DTPa-HBV-IPV/Hib (PHiD-CV/Hx group), or DTPa-HBV-IPV/Hib alone (Control group). Solicited and unsolicited adverse events (AEs) (any and grade 3) were recorded within 4 days and 31 days post-vaccination, respectively. Serious AEs (SAEs) were recorded throughout the study. Safety analyses were carried out on the total vaccinated cohort. Results: Between February and July 2011, 300 infants were enrolled; 298 received between one and three vaccine doses (PHiD-CV/Hx group: n = 199; Control group: n = 99). Within 31 days post-vaccination, 8.2% and 3.0% of overall doses in the PHiD-CV/Hx and Control groups, respectively, were followed by ≥1 grade 3 AE (solicited and/or unsolicited, local and/or general). Within 4 days post-vaccination, the most frequent solicited local symptom was pain (PHiD-CV/Hx group: 48.9% of doses; Control group: 31.0% of doses) and the most frequent solicited general symptom was irritability (PHiD-CV/Hx group: 58.0% of doses; Control group: 40.4% of doses). The most frequent grade 3 local symptom was pain; following 6.5% and 1.0% of doses in the PHiD-CV/Hx and Control groups, respectively. Grade 3 solicited general symptoms were uncommon in both groups (PHiD-CV/Hx group: ≤1.9% of doses; Control group: ≤0.3% of doses). Unsolicited symptoms were reported following 12.3% and 14.8% of doses in the PHiD-CV/Hx and Control groups, respectively. Grade 3 unsolicited symptoms were reported following ≤0.3% of doses; none were considered related to vaccination. Fifteen infants reported ≥1 SAE (PHiD-CV/Hx group: 9/199; Control group: 6/99); none were fatal; none were considered related to vaccination. Conclusion: A PHiD-CV 3-dose primary vaccination, co-administered with DTPa-HBV-IPV/Hib at 2, 3 and 4 months of age was well tolerated by Vietnamese infants. PHiD-CV reactogenicity was comparable to that observed in other South-East Asian populations.1,2 1Chevallier PIDJ 2009;28:S109-18. 2Kim PIDJ 2011;30:e235-43.