The development of a new heptavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C vaccine: a randomized dose-ranging trial of the conjugate vaccine components.
OBJECTIVE
To assess immunogenicity, antibody persistence, immune memory, and reactogenicity of a novel heptavalent DTPw-HBV/Hib-MenAC (diphtheria, tetanus, whole cell pertussis-hepatitis B virus/Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C) vaccine.


METHODS
This was an open, randomized study in the Philippines, with DTPw-HBV/Hib-MenAC administered at 6, 10, and 14 weeks of age. Three different polysaccharide contents of the conjugate vaccine components were assessed with conjugated PRP (polyribosylribitol phosphate), MenA, and MenC polysaccharides at the following doses: 2.5 microg of each, 5 microg of each, or 2.5 microg of PRP and 5 microg each of MenA and MenC. Controls received licensed DTPw-HBV and Hib or DTPw-HBV/Hib and MenC conjugate vaccines separately. Immune memory was evaluated via plain polysaccharide challenge administered to half of the subjects at 10 months of age.


RESULTS
After primary vaccination, at least 97.7% of DTPw-HBV/Hib-MenAC recipients had serum bactericidal antibody (SBA)-MenA and SBA-MenC titers > or =1:8, and at least 99% had anti-PRP antibody concentrations > or =0.15 microg/ml. Immune responses to DTPw-HBV components were not impaired by the lowest dose of Hib-MenAC vaccine. Plain polysaccharide challenge induced marked increases in Hib, MenA, and MenC antibodies in primed subjects, indicative of immune memory. All of the experimental vaccines were well tolerated.


CONCLUSIONS
The lowest dose of DTPw-HBV/Hib-MenAC polysaccharide conjugate vaccine was well tolerated, immunogenic, had good persistence of antibodies, and demonstrated immune memory, and consequently was selected for further development.
Gatchalian
S
S
Research Institute for Tropical Medicine, Alabang, Muntinlupa, Philippines.
Palestroque
E
E
De Vleeschauwer
I
I
Han
H H
HH
Poolman
J
J
Schuerman
L
L
Dobbelaere
K
K
Boutriau
D
D
D000907:Antibodies, Bacterial / Q000097:blood; D004165:Diphtheria / Q000517:prevention & control; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; 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; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D038381:Neisseria meningitidis, Serogroup A / Q000276:immunology; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology; D013742:Tetanus / Q000517:prevention & control; D016896:Treatment Outcome; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control
D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D022401:Meningococcal Vaccines; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate