In Vietnam, the reactogenicity and safety of a new vaccine need to be evaluated in the local target population before the vaccine can be registered in the country. In the present study, the reactogenicity and safety profile of PHiD-CV co-administered with DTPa-HBV-IPV/Hib in Vietnamese infants seemed in line with that observed in previous studies, in which PHiD-CV was co-administered with routine childhood vaccines [13, 21–23].
Within the 31-day post-vaccination period, 8.2% of overall doses were followed by at least one grade 3 symptom (solicited and/or unsolicited, local and/or general) in the infants who received PHiD-CV co-administered with DTPa-HBV-IPV/Hib, while this was 3.0% of overall doses in the infants who received DTPa-HBV-IPV/Hib alone. This difference was mainly due to the higher proportion of doses followed by grade 3 pain during the 4-day post-vaccination period in the infants who received both vaccines co-administered compared with those who received DTPa-HBV-IPV/Hib alone (6.5% [95% CI: 4.7, 8.8] versus 1.0% [95% CI: 0.2, 2.9] of overall doses). This difference in incidence of pain was not unexpected and could be explained by the fact that the infants of the PHiD-CV group had 2 injections at each vaccination visit while those in the Control group had only 1 injection per visit. The most frequently reported grade 3 solicited general symptom in the infants who received PHiD-CV co-administered with DTPa-HBV-IPV/Hib was irritability, which was reported following 1.9% (95% CI: 0.9, 3.4) of doses. The use of antipyretic medication was low in both groups and grade 3 fever was only reported in one infant vaccinated with DTPa-HBV-IPV/Hib alone.
The incidence and nature of the grade 3 solicited symptoms reported in this study were in line with those reported in a previous study assessing the co-administration of PHiD-CV and DTPa-HBV-IPV/Hib in Taiwanese infant. In that study, the most frequently reported grade 3 solicited local and general symptoms were pain (following 4.2% of doses [95% CI: 2.8, 6.0]) and irritability (following 6.3% of doses [95% CI: 4.6, 8.4]) . In another study, in which PHiD-CV was co-administered with a monovalent vaccine against Hib in Korean infants, grade 3 solicited symptoms were reported following no more than 2.6% of doses, which seems slightly lower than the reporting rates observed in the present study . When compared to co-administration of PHiD-CV and DTPa-based or Hib vaccines, the incidence of grade 3 symptoms seemed higher when PHiD-CV was co-administered with whole cell pertussis-based combination vaccines, as observed in 2 Asian studies, in which the incidence of grade 3 pain reached 9.4% (95% CI: 6.4, 13.3) and 27.7% (95% CI: 24.4, 31.1) of doses and grade 3 irritability, 2.9% (95% CI: 1.9, 4.2) and 8.3% (95% CI: 6.4, 10.6) of doses in infants in the Philippines and India, respectively [13, 23]. This observation was expected since whole cell pertussis-based vaccines are known to induce more adverse events than DTPa-based vaccines .
In the present study, pain was the most frequently reported solicited local symptom with any intensity, which was reported following 48.9% (95% CI: 44.8, 53.0) of PHiD-CV doses co-administered with DTPa-HBV-IPV/Hib. In contrast, redness was the most common solicited local symptom in previous Asian studies conducted in Taiwan and Korea, in which PHiD-CV was also co-administered with DTPa-based vaccines [21, 22]. In the previous studies conducted in India and the Philippines, pain was also the most common solicited local symptom following co-administration of PHiD-CV and whole cell pertussis-based vaccines (following 71.0% of doses [95% CI: 67.6, 74.4] and 67.2% of doses [95% CI: 64.0, 70.3]) [13, 23]. The incidence of solicited local symptoms was comparable at both injections sites in the infants who received PHiD-CV co-administered with DTPa-HBV-IPV/Hib, but solicited local and general symptoms seemed more frequently reported in infants who received PHiD-CV in addition to DTPa-HBV-IPV/Hib than in those who received DTPa-HBV-IPV/Hib alone.
The percentage of doses followed by at least one unsolicited adverse event within the 31-day post-vaccination period was comparable in both groups and the incidences of grade 3 unsolicited symptoms were low. Unsolicited symptoms causally related to vaccination were only reported in one child in each group. Throughout the study, 15 infants (9/199 infants in the PHiD-CV group and 6/99 infants in the Control group) reported at least one SAE. None of these SAEs were fatal or considered by the investigator to be causally related to vaccination.
This study had a very high compliance rate since 97.0% of the infants who received PHiD-CV co-administered with DTPa-HBV-IPV/Hib and all the infants vaccinated with DTPa-HBV-IPV/Hib alone received the 3 vaccine doses. However, potential limitation of the study included its non-blinded (open) design, due to the different number of injections in both groups. The open design might have induced a bias in the reactogenicity and safety profile towards increased reporting of AEs in infants in the PHiD-CV group since their parents or LARs and the investigators were aware that they had received a new vaccine in addition to the antigens received by the infants in the Control group. Another limitation of this study was the fact that there were no confirmatory analyses with regards to the reactogenicity and safety objectives. Due to above mentioned limitations, the study results should be interpreted with caution.