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

BackgroundPneumococcal 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.MethodsThis 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.ResultsWithin 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.ConclusionsPHiD-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 registrationClinicalTrials.gov: http://NCT01153841

The emerging physiological roles of the glycerophosphodiesterase family

“…Based on this evidence, in animal models, protein D has been used as an active vaccine against homologous and heterologous strains . The pneumococcal conjugate vaccine (Synflorix™; GlaxoSmithKline, Rixensart, Belgium) that has been licensed in Europe and in more than 110 countries around the world since 2008 is a 10‐valent vaccine that uses a nonlipidated form of nontypeable H. influenzae protein D as the protein carrier component . The antibodies raised by the protein D vaccine inhibit the enzymatic activity of recombinant protein D in in vitro assays, and the measurement of these antibody responses from serum samples is a useful tool for assessing the level of vaccine‐induced protective immunity .…”

A 6-year safety surveillance of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in South Korea

“…8,11 Safety results were also comparable to those seen in a phase III randomized clinical trial of PHiD-CV co-administered with the diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus and Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/HiB) in Vietnamese infants; i.e., pain at injection site, irritability and fever were the most common local and general AEs, respectively, seen in the PHiD-CV group, with no SAEs causally related to the vaccine. 18 PHiD-CV was proven to be well tolerated and generally as immunogenic in preterm infants as in term infants when given as a 3-dose primary vaccination followed by a booster dose. Incidences of fever and other solicited general symptoms were generally similar.…”

Reações de hipersensibilidade a vacinas

“…Overall, pneumococcal vaccines are well tolerated, with more local adverse events being reported. 41,42 Two cases of anaphylaxis associated with the 23-valent pneumococcal polysaccharide vaccine were reported in children, in 2001 and 2010; in both, immediate-read skin tests demonstrated sensitization to pneumococcal polysaccharides. These cases highlight that hypersensitivity reactions to the vaccine antigen are rare events, and their confirmation is challenging in clinical practice.…”