Functional antibody activity elicited by fractional doses of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate)

We evaluated the functional activities of antibodies, serum bactericidal ac tivity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using so dium thiocyanate (NaSCN) elution, elicited after vaccination with fractiona l doses of the Haemophilus influenzae type b conjugate (polyribosylribitol phosphate [PRP] conjugated to tetanus toxoid [PRP-T]) vaccine. A cohort of 600 infants from the Dominican Republic were randomized to receive one of t hree regimens of the PRP-T vaccine at ages 2, 4, and 6 months: full doses ( 10 mug of PRP antigen), one-half doses (5.0 mug), and one-third doses (3.3 mug) (J. Fernandez et al., Am. J. Trop. Med. Hyg. 62:485-490, 2000). Sixty serum samples, collected at age 7 months, with greater than or equal to2.0 mug of anti-PRP IgG per ml were randomly selected for avidity determination s. Geometric mean IgG concentrations were 13, 14, and 17 mug/ml for infants who received the full-dose (n = 19), one-half-dose (n = 19), and one-tbird -dose (n = 22) regimens, respectively. SBA geometric mean titers (1/dilutio n) were 85.0, 82.0, and 76.1 in sera from infants receiving the full-, one- half-, and one-third-dose regimens, respectively. Avidity indices (mean +/- standard error weighted average of NaSCN molar concentration x serum dilut ion factor) were 71.9 +/- 9.4, 123.6 +/- 26.8, and 150.9 +/- 24.9 for the f ull-, one-half-, and one-third-dose regimens, respectively. Upon comparison , the only significant difference (P = 0.024) found was a greater avidity i ndex for sera from infants receiving the one-third-dose regimen than for se ra from infants receiving the the full-dose regimen. We conclude that fract ional doses elicit similar functional antibody activities in infants with 2 jig of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants re ceiving three doses of either the full concentration or one-half or one-thi rd of the labeled concentration, respectively. This approach offers an alte rnative strategy for the prevention of H. influenzae type b disease in coun tries with limited resources.