Avidity and Bactericidal Activity of Specific IgG Antibody Elicited by Immunization Against Haemophilus influenzae type b (Hib) with a Combined DTaP-Hib-Hepatitis B Vaccine in Infants ♦ 929

Abstract

We previously showed that a diphtheria and tetanus toxoids with acellular pertussis (DTaP) vaccine when combined with Haemophilus influenzae b(Hib) polysaccharide (PRP) conjugated to tetanus toxoid (PRP-T) vaccine and Hepatitis B (HB) vaccine as a single injection: (1) does not produce equivalent anti-PRP antibody levels to those achievable with separate injections in infants following a three dose primary sequence at 2, 4 and 6 months of age; but (2) vaccinees producing low or undetectable anti-PRP antibody responses achieve high-titered, IgG-predominant responses when given a booster of PRP-conjugate (CRM197-OS) vaccine 3-7 months later, suggestive of a memory response (Clin Infect Dis 1997;25:1378-1384). Here, we assessed the avidity and bactericidal activity (BA) of the sera from these infants to further characterize the immunologic responses and the functional capacity of the antibodies produced. Avidity of the anti-PRP antibody was quantitated by use of a chaotropic agent (2.5-6.0M urea) in an ELISA with results expressed as percent of antibody bound to PRP after chaotropic exposure. BA was measured by a standard in vitro assay with wild Hib (strain Eagan). CBER lot 1983 anti-PRP antisera was used as a reference for both assays. Avidity and BA of 39 sera (post primary DTaP-PRP-T-HB combined vaccine, pre-CRM197-OS boost and post-boost) from infants with anti-PRP antibody levels 1.0 μg/ml. In vaccinees with 1 μg/ml of IgG anti-PRP antibody the post primary value was 66% (61-71%) and for the CBER standard it was 59% (53-65%); 1 μg/ml group post primary (p<0.001). BA of the anti-PRP antibody was correlated with total anti-PRP IgG antibody (r=0.61, p<0.001). We conclude that despite low post priming anti-PRP antibody levels, the studied DTaP-PRP-T-HB combination vaccine (manufactured by SmithKline Beecham) elicits antibody of high avidity, affinity maturation as seen in memory responses appears to occur in the absence of further antigen exposure from post primary to pre-boost even in those with very low anti-PRP antibody, and the elicited anti-PRP antibody is bactericidal.