Early responses to nonconjugated polyribosylribitol phosphate challenge asevidence of immune memory after combined diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b primary vaccination

Objectives. A high risk of invasive Haemophilus influenzae type b (Hib) dis ease exists in the first few years of life. A reduction in anti-polyribosyl ribitol phosphate (PRP) antibody concentrations follows the administration of certain diphtheria-tetanus-acellular pertussis (DTPa)-based Hib conjugat e combined vaccines. However, these combined vaccines prime the immune memo ry, which is an important factor in protection. As yet there is no direct e vidence of the time scale involved in the development of the immune memory post-primary vaccination. In this report we investigated the presence of im mune memory at 10 and 12 months of age, 4 and 6 months after primary vaccin ation of young infants with a pentavalent combination of DTPa, inactivated poliovirus vaccine (IPV) and Hib (DTPa-IPV/Hib) vaccine. Methods. In two trials (A and B) infants received DTPa-IPV combined with Hi b-tetanus conjugate (PRP-T) vaccine at 2, 4 and 6 months of age. The presen ce of immune memory was assessed by measuring anti-PRP concentrations 7 to 10 days after a nonconjugated PRP challenge given at 10 months in Trial A a nd at 12 months in Trial B. Results. Administration of a nonconjugated PRP challenge 4 and 6 months aft er primary vaccination in Trials A and B, respectively, elicited an increas e in anti-PRP geometric mean concentrations (4.5 and 5.8 mug/ml, respective ly) within 7 to 10 days. These concentrations exceed those reported in the literature involving unprimed children who had received a single dose of no nconjugated PRP at the same age. Conclusion. The results demonstrate the development of anti-PRP immune memo ry at an early age, 4 and 6 months after completion of a three dose primary vaccination course of combined DTPa-IPV/Hib vaccine. The ability of primed infants to mount a rapid response is an important observation given the hi gh risk of Hib infection at this critical age.