Interchangeability of Haemophilus influenzae type b vaccines in the primary series: evaluation of a two-dose mixed regimen.
OBJECTIVE
To evaluate two- or three-dose "mixed" regimens of Haemophilus influenzae type b conjugate vaccines in the priming series.


METHODS
Two randomized clinical trials with 140 and 181 infants, respectively.


METHODS
Private practices in New Orleans and Chicago.


METHODS
In trial I, infants received one of four regimens. Two were recommended regimens for polyribosylribitol phosphate (PRP)-meningococcal protein conjugate (M) and PRP-tetanus toxoid conjugate (T). Two mixed regimens consisted of M at 2 months followed by two doses of T or PRP-diphtheria toxoid conjugate (D) at 4 and 6 months. Trial II consisted of three groups. Two were recommended regimens for M and T. The third was a two-dose mixed regimen consisting of M at 2 months and T at 4 months. Parents were interviewed and instructed to record side effects after each vaccination. Serum was assayed for H influenzae type b anticapsular antibody (anti-PRP).


RESULTS
Minor differences in safety profiles likely reflected alpha error. In trial I, M (lot 0884T, one of several known to have had decreased immunogenicity), probably primed for substantial increase in serum antibody when D or T was given at 4 and 6 months. In trial II, infants who received the two-dose mixed regimen (M from immunogenic lot 0116W at 2 months and T at 4 months) had a significantly higher mean area under the curve than recipients of the three-dose TTT regimen when antibody concentration was plotted against age, although the geometric mean anti-PRP antibody concentration for the MT-recipients was significantly lower at 7 months.


CONCLUSIONS
M used in trial I may have primed infants despite poor immunogenicity. The two-dose mixed regimen (MT-) in trial II produced a mean anti-PRP antibody concentration with higher sustained anti-PRP concentrations from 2 to 7 months, as judged by the area under the curve, but a lower mean anti-PRP antibody concentration at 7 months.
Department of Pediatrics, University of Chicago, IL, USA.
K M
KM
Bewley
J G
JG
Schwab
G A
GA
Ballanco
R S
RS
Daum
D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D016667:Bacterial Capsules / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects; D004168:Diphtheria Toxoid / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines; D011134:Polysaccharides / Q000008:administration & dosage* / Q000009:adverse effects; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage* / Q000009:adverse effects; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000009:adverse effects; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004168:Diphtheria Toxoid; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; C044237:Haemophilus influenzae type b polysaccharide vaccine; C052180:Haemophilus influenzae type b-polysaccharide vaccine-diphtheria toxoid conjugate; D022401:Meningococcal Vaccines; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C008984:polyribitol phosphate