title: Functional antibody activity elicited by fractional doses of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate).
abstract: We evaluated the functional activities of antibodies, serum bactericidal activity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using sodium thiocyanate (NaSCN) elution, elicited after vaccination with fractional 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 three regimens of the PRP-T vaccine at ages 2, 4, and 6 months: full doses (10 microg of PRP antigen), one-half doses (5.0 microg), and one-third doses (3.3 microg) (J. Fernandez et al., Am. J. Trop. Med. Hyg. 62:485-490, 2000). Sixty serum samples, collected at age 7 months, with > or =2.0 microg of anti-PRP IgG per ml were randomly selected for avidity determinations. Geometric mean IgG concentrations were 13, 14, and 17 microg/ml for infants who received the full-dose (n = 19), one-half-dose (n = 19), and one-third-dose (n = 22) regimens, respectively. SBA geometric mean titers (1/dilution) 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 dilution factor) were 71.9 +/- 9.4, 123.6 +/- 26.8, and 150.9 +/- 24.9 for the full-, one-half-, and one-third-dose regimens, respectively. Upon comparison, the only significant difference (P = 0.024) found was a greater avidity index for sera from infants receiving the one-third-dose regimen than for sera from infants receiving the the full-dose regimen. We conclude that fractional doses elicit similar functional antibody activities in infants with > or = 2 microg of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants receiving three doses of either the full concentration or one-half or one-third of the labeled concentration, respectively. This approach offers an alternative strategy for the prevention of H. influenzae type b disease in countries with limited resources.
authors.affiliation: Immunology Section, Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. sxs8@cdc.gov
authors.forename: S
authors.initials: S
authors.lastname: Romero-Steiner
authors.forename: J
authors.initials: J
authors.lastname: Fernandez
authors.forename: C
authors.initials: C
authors.lastname: Biltoft
authors.forename: M E
authors.initials: ME
authors.lastname: Wohl
authors.forename: J
authors.initials: J
authors.lastname: Sanchez
authors.forename: J
authors.initials: J
authors.lastname: Feris
authors.forename: S
authors.initials: S
authors.lastname: Balter
authors.forename: O S
authors.initials: OS
authors.lastname: Levine
authors.forename: G M
authors.initials: GM
authors.lastname: Carlone
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D015331:Cohort Studies; D003906:Developing Countries; D004168:Diphtheria Toxoid / Q000008:administration & dosage* / Q000191:economics / Q000276:immunology*; D004293:Dominican Republic; D006192:Haemophilus Infections / Q000276:immunology / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000191:economics / Q000276:immunology*; D006193:Haemophilus influenzae / Q000276:immunology*; D017048:Health Care Costs; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D018073:Haemophilus Vaccines; C052180:Haemophilus influenzae type b-polysaccharide vaccine-diphtheria toxoid conjugate; D007074:Immunoglobulin G