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

Abstract

A high risk of invasive Haemophilus influenzae type b (Hib) disease exists in the first few years of life. A reduction in anti-polyribosylribitol phosphate (PRP) antibody concentrations follows the administration of certain diphtheria-tetanus-acellular pertussis (DTPa)-based Hib conjugate combined vaccines. However, these combined vaccines prime the immune memory, which is an important factor in protection. As yet there is no direct evidence of the time scale involved in the development of the immune memory post-primary vaccination. In this report we investigated the presence of immune memory at 10 and 12 months of age, 4 and 6 months after primary vaccination of young infants with a pentavalent combination of DTPa, inactivated poliovirus vaccine (IPV) and Hib (DTPa-IPV/Hib) vaccine. In two trials (A and B) infants received DTPa-IPV combined with Hib-tetanus conjugate (PRP-T) vaccine at 2, 4 and 6 months of age. The presence 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 and at 12 months in Trial B. Administration of a nonconjugated PRP challenge 4 and 6 months after primary vaccination in Trials A and B, respectively, elicited an increase in anti-PRP geometric mean concentrations (4.5 and 5.8 microg/ml, respectively) within 7 to 10 days. These concentrations exceed those reported in the literature involving unprimed children who had received a single dose of nonconjugated PRP at the same age. The results demonstrate the development of anti-PRP immune memory 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 high risk of Hib infection at this critical age.