Haemophilus influenzaeType b Immunization in Infants in the United Kingdom: Effects of Diphtheria/Tetanus/Acellular Pertussis/Hib Combination Vaccine, Significant Prematurity, and a Fourth Dose

OBJECTIVE: To measure anti-polyribosylribitolphosphate (PRP) antibody and anti-tetanus toxoid (TT) antibody responses in UK infants to explore the effects of (1) immunization with an acellular diphtheria/tetanus/pertussis/Haemophilus influenzae type b (DTPHib) combination vaccine, (2) significant preterm delivery, and (3) a fourth dose of conjugated Hib vaccine (PRP-T) in those with a low anti-PRP antibody (<1.0 microg/mL) after primary immunization. METHODS: A prospective study was conducted in 4 tertiary neonatal units at a time when 2 types of DTPHib vaccines were used interchangeably in the United Kingdom for primary immunization: acellular (DTPaHib) and whole cell. Timing and type of all vaccine doses were as per standard UK practice. Blood was taken before and after immunization. A total of 166 preterm and 45 term infants completed the study; 97 (15 term) infants who had anti-PRP antibody <1.0 microg/mL were offered a fourth dose of PRP-T; 61 (55 preterm) then had repeat antibody measurements. Anti-PRP and anti-TT antibody after primary immunization relative to gestation and number of whole cell vaccine doses received was measured, as well as anti-PRP antibody after a fourth dose of PRP-T. RESULTS: A total of 49% of preterm and 33% of term infants had anti-PRP antibody <1.0 microg/mL after full primary immunization. Receipt of 1 or more acellular vaccine doses was associated with lower anti-PRP antibody, a dose response effect being observed. Preterm infants were less likely to have anti-PRP antibody >1.0 microg/mL compared with term infants. A total of 93% of infants who were given a fourth dose had anti-PRP antibody >1.0 microg/mL. Anti-TT antibody responses were satisfactory for all infants but also reduced by each DTPaHib dose received. CONCLUSION: Infants who receive DTPaHib, are significantly preterm, or who do not receive a fourth dose of conjugated Hib vaccine may be at increased risk for Hib disease.