Adverse reactions after any of the conjugate Hib vaccines are uncommon, are typically mild and usually resolve within 12 to 24 h.12 A randomized, blinded, comparative study found only minor differences among the four vaccines in the frequency and duration of adverse reactions.13
All four conjugate Hib vaccines are highly immunogenic in adults and older children. However, they differ markedly in the immune responses they stimulate among infants.13-16
PRP-OMP is unique among the conjugate Hib vaccines in producing substantial antibody rises after the first dose, given at 2 months of age.13 However, there is only a modest further increase in antibody after the second dose (or after a third dose).13 Consequently PRP-OMP is licensed in the United States as a two-dose primary series, whereas PRP-CRM and PRP-T are licensed as a three-dose primary series.
With the near-elimination of invasive Hib disease after widespread use of conjugate Hib vaccines in infancy, the three vaccines have been considered interchangeable for primary as well as booster vaccination.24 However, after Alaska's change in 1996 from use of PRP-OMP to use of a combination product containing PRP-CRM plus diphtheria and tetanus toxoids and whole cell pertussis vaccine, the Centers for Disease Control and Prevention noted a 2- to 4-fold increase in invasive Hib disease (1995, 2 cases; 1996, 6 cases; 1997, 7 cases).25, 26 Subsequent evaluation of oropharyngeal carriage of Hib among native Alaskan children found carriage rates ranging from 5.6% among children ages 1 to 2 years, to 13.6% among those age 5 to 6 years.21 Although the rates of invasive Hib disease remain low the rates of carriage do not, and concern has been raised that these findings may be a result of the change from PRP-OMP to PRP-CRM. If so, use of PRP-OMP (at least for the first dose) might be more prudent in particularly high risk populations.
The conjugate Hib vaccines are associated with few and mild adverse reactions in all age groups. All are highly immunogenic in older children and adults; they show differing immunogenicities when used for primary immunization of infants: PRP-D is of low immunogenicity and is not suitable for infant use except in highly immunized populations with low Hib prevalence; PRP-OMP is immunogenic after only a single dose, but antibody concentrations after completion of the primary series are lower than those obtained with PRP-T and PRP-CRM. The latter two vaccines produce little antibody after the first two injections and may not be the best choice in populations characterized by high attack rates of Hib disease early in infancy, but they produce substantially higher final antibody concentrations than PRP-OMP after completion of the primary series and might be preferable in populations not marked by early, intense Hib activity. The vaccines are acceptably interchangeable during the primary series, and indeed a sequence in which one injection of PRP-OMP is used followed by two of PRP-T or PRP-CRM appears to provide the optimum antibody response.
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FIRST INTERNATIONAL CONFERENCE ON HAEMOPHILUS INFLUENZAE TYPE b INFECTION IN ASIA
The Editors thank the Association pur l'Aide à la Médicine Préventive, the Foundation Mérieux, and the World Health Organization for supporting publication of these proceedsings, and Jennifer Wells for her editorial assistance.