Safety and reactogenicity of primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Vietnamese infants: a randomised, controlled trial

Abstract

Background: Pneumococcal infections are major causes of child mortality and morbidity worldwide and antibiotic resistance of Streptococcus pneumoniae is a major concern, especially in Asian countries. The present study was designed to evaluate the reactogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the licensed diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus and H. influenzae type b vaccine (DTPa-HBV-IPV/Hib) in a 3-dose primary vaccination course in Vietnamese infants.

Methods: This phase III, open, randomised study was conducted in one centre in Ho Chi Minh City between February and July 2011. Healthy infants (N=300) were randomised (2:1) to receive either PHiD-CV co-administered with DTPa-HBV-IPV/Hib (PHiD-CV group) or DTPa-HBV-IPV/Hib alone (Control group) at 2, 3, and 4 months of age.

Results: Within 31 days post-vaccination, 8.2% of overall doses in the PHiD-CV group and 3.0% of overall doses in the Control group were followed by at least one solicited and/or unsolicited, local and/or general adverse event of grade 3 intensity. Pain at injection site was the most common grade 3 solicited symptom, which was reported following 6.5% and 1.0% of overall doses in the PHiD-CV and Control groups, respectively. Within 4 days post-vaccination, the most common solicited local and general symptoms reported with any intensity were pain (48.9% and 31.0% of doses in the PHiD-CV and Control groups) and irritability (58.0% and 40.4% of doses in the PHiD-CV and Control groups). Within 31 days post-vaccination, the incidence of unsolicited symptoms was comparable in both groups (following 12.3% and 14.8% of doses in the PHiD-CV and Control groups, respectively). Throughout the study, 13 serious adverse events (SAEs) were reported in 9 infants in the PHiD-CV group and 11 SAEs in 6 infants in the Control group. None of them were fatal or considered causally related to vaccination.

Conclusions: PHiD-CV had a clinically acceptable safety profile when co-administered with DTPa-HBV-IPV/Hib in Vietnamese infants. The reactogenicity of PHiD-CV was comparable to that observed in other South-East Asian populations.

Trial registration: ClinicalTrials.gov NCT01153841.

Figures

Figure 1

Trial profile. Footnote: PHiD-CV group= infants vaccinated with PHiD-CV co-administered with DTPa-HBV-IPV/Hib at 2, 3, and 4 months of age. Control group= infants vaccinated with DTPa-HBV-IPV/Hib at 2, 3, and 4 months of age. N= number of infants.

Figure 2

Percentages of doses followed by pain (A), redness (B), and swelling (C) at the specified injection site of any intensity and grade 3 intensity reported during the 4-day post-vaccination period (total vaccinated cohort). Footnote: PHiD-CV group= infants vaccinated with PHiD-CV co-administered with DTPa-HBV-IPV/Hib at 2, 3, and 4 months of age. Control group= infants vaccinated with DTPa-HBV-IPV/Hib at 2, 3, and 4 months of age. Grade 3 symptoms: pain if the infant was crying when the limb was moved or if the limb was spontaneously painful and redness or swelling if the diameter was >30 mm. Error bars indicate 95% confidence intervals.

Figure 3

Incidence of overall per dose solicited local (pain, redness, and swelling) and general (drowsiness, fever, irritability, and loss of appetite) symptoms of any intensity and grade 3 intensity reported during the 4-day post-vaccination period (total vaccinated cohort). Footnote: PHiD-CV group= infants vaccinated with PHiD-CV co-administered with DTPa-HBV-IPV/Hib at 2, 3, and 4 months of age. Control group= infants vaccinated with DTPa-HBV-IPV/Hib at 2, 3, and 4 months of age. Grade 3 symptoms: pain if the infant was crying when the limb was moved or if the limb was spontaneously painful, redness or swelling if the diameter was >30 mm, drowsiness if it prevented normal activity, fever if axillary temperature was >39.5°C, irritability if the infant was crying and could not be comforted or if it prevented normal activity, and loss of appetite if the infant did not eat at all. Error bars indicate 95% confidence intervals.

Figure 4

Percentages of doses followed by drowsiness (A), fever (B), irritability (C), and loss of appetite (D) of any intensity and grade 3 intensity reported during the 4-day post-vaccination period (total vaccinated cohort). Footnote: PHiD-CV group= infants vaccinated with PHiD-CV co-administered with DTPa-HBV-IPV/Hib at 2, 3, and 4 months of age. Control group= infants vaccinated with DTPa-HBV-IPV/Hib at 2, 3, and 4 months of age. Grade 3 symptoms: drowsiness if it prevented normal activity, fever if axillary temperature was >39.5°C, irritability if the infant was crying and could not be comforted or if it prevented normal activity, and loss of appetite if the infant did not eat at all. Error bars indicate 95% confidence intervals.