Immunogenicity, reactogenicity and safety of three-dose primary and booster vaccination with combined diphtheria-tetanus-whole-cell pertussis-hepatitis B-reduced antigen content Haemophilus influenzae type b vaccine in Filipino children.
OBJECTIVE
To evaluate the immunogenicity, reactogenicity and safety of primary and booster vaccination with DTPw-HBVLT/Hib2.5 vaccine containing low thiomersal and reduced quantities of Hib polysaccharide (PRP).


BACKGROUND
Combined DTP vaccines have high global coverage. Thus, the addition of new antigens to existing DTP vaccines is the most effective way to ensure high coverage.


METHODS
192 healthy infants were randomized to receive the investigational DTPw-HBVLT/Hib2.5 vaccine or licensed DTPw-HBV/Hib10 at 6, 10, 14 weeks. Immune memory to the Hib antigen was assessed through administration of plain PRP challenge at 10 months in 50% of subjects. Challenged and unchallenged subjects respectively received a DTP-HBV or DTPa-HBV/Hib booster at 15-18 months of age. Antibody responses were measured using enzyme-linked immunosorbent assay (ELISA) and reactogenicity was assessed using diary cards.


RESULTS
One month post-primary vaccination, 100% and ≥ 93.7% of subjects in both groups had anti-PRP antibody concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL, respectively. Robust responses to PRP were observed after the 10 month plain PRP challenge and booster responses were observed in unchallenged subjects after the booster dose at 15-18 months of age. Post-primary and post-booster responses to the other vaccine antigens were at least as high in the DTPw-HBVLT/Hib2.5 group versus the DTPw-HBV/Hib10 group. The reactogenicity profile of the DTPw-HBVLT/Hib2.5 vaccine was acceptable.


CONCLUSIONS
The DTPw-HBVLT/Hib2.5 combination vaccine with reduced thiomersal and Hib content had equivalent immunogenicity and tolerability versus the full standard DTPw-HBV/Hib10 vaccine. DTPw-HBVLT/Hib2.5 or DTPw-HBV/Hib10 vaccines can contribute to reducing childhood diseases through ensuring high vaccine coverage in mass vaccination programs. ClinicalTrials.gov identifiers: NCT 01061541, NCT00158808.
Gatchalian
Salvacion R
SR
Research Institute for Tropical Medicine, DOH Compound, Alabang, Muntinlupa City, Philippines. sally.r.gatchalian@gsk.com
Ramakrishnan
Gunasekaran
G
Bock
Hans L
HL
Lefevre
Inge
I
Jacquet
Jeanne M
JM
D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004165:Diphtheria / Q000517:prevention & control; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006192:Haemophilus Infections / Q000517:prevention & control; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D019741:Haemophilus influenzae type b / Q000276:immunology; D006509:Hepatitis B / Q000517:prevention & control; D006511:Hepatitis B Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D010679:Philippines; D013742:Tetanus / Q000517:prevention & control; D016896:Treatment Outcome; D014611:Vaccination; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control
D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D006511:Hepatitis B Antigens; D017325:Hepatitis B Vaccines; D017778:Vaccines, Combined; C080881:diphtheria-tetanus-pertussis-haemophilus b conjugate vaccine