CLINICAL ACCEPTABILITY AND IMMUNOGENICITY OF A PENTAVALENT PARENTERALCOMBINATION VACCINE CONTAINING DIPHTHERIA, TETANUS, ACELLULAR PERTUSSIS, INACTIVATED POLIOMYELITIS AND HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE ANTIGENS IN 2, 4 AND 6-MONTH-OLD CHILEAN INFANTS

Background. In recent years additional parenteral vaccines have been r ecommended for routine immunization of infants in the US and elsewhere . The ability to administer multiple vaccines as a single injection wi thout unacceptably increasing reactogenicity or decreasing immunogenic ity of any component would offer many practical advantages. Methods. A randomized, open, controlled trial was conducted to assess the tolera nce profile and immunogenicity, as well as to identify potential antig enic interferences, resulting from administration of a parenteral comb ination vaccine for infants. The vaccine contains diphtheria and tetan us toxoids, acellular pertussis antigens (DTaP), enhanced inactivated poliovirus (eIPV) and Haemophilus influenzae type b-tetanus toroid con jugate (PRP-T). Infants (n = 711) were randomly assigned to receive 1 of 5 regimens as the primary series at 2, 4 and 6 months of age, by gr oup: (1) DTaP plus oral polio vaccine (OPV); (2) DTaP plus eIPV (separ ate injections); (3) DTaP-eIPV combined as a single injection; (4) DTa P-eIPV combined, plus a separate injection of PRP-T; or (5) DTaP-eIPV combined and reconstituting PRP-T, as a single injection. At 3, 5 and 7 months Groups 1, 2 and 3 received PRP-T. At 12 months all infants re ceived a booster doss of DTaP reconstituting PRP-T as a single injecti on, plus a separate injection of measles, mumps and rubella vaccine. G roups 2, 3, 4 and 5 received OPV at 7 months, and all infants received OPV at 13 months. Serum immune responses were measured to the primary series at 2 and 7 months and to the booster dose at 12 and 13 months, Results. Reaction rates were similar among groups. In the primary ser ies combining eIPV with DTaP decreased geometric mean titers (GMTs) to diphtheria, tetanus and pertussis, In addition concomitant PRP-T (eit her simultaneous or combined) with DTaP-eIPV lowered anti-PRP and furt her decreased tetanus GMTs. Nonetheless in 100% of infants protective titers were achieved against diphtheria and tetanus (>0.01 IU/ml each) and against the poliovirus types 1, 2 and 3 after eIPV (Groups 2 to 5 ); 99% of infants (Groups 4 and 5) had protective titers against PRP ( greater than or equal to 0.15 mu g/ml). After boosting with DTaP/PRP-T decreased GMTs to diphtheria and PRP antigens were observed in the gr oups that received DTaP and eIPV combined. Nonetheless protective tite rs to diphtheria, tetanus and PRP occurred consistently. In contrast c oncomitant PRP-T with DTaP-eIPV enhanced the pertussis GMTs. Conclusio ns. We conclude that combined DTaP, eIPV and PRP-T in a single injecti on is well-tolerated and elicits an acceptable immune response to each component.