Serotype-specific hyporesponsiveness to pneumococcal conjugate vaccine in infants carrying pneumococcus at the time of vaccination.

OBJECTIVE: To determine whether pneumococcal carriage at the time of 11-valent pneumococcal conjugate vaccine (PCV-11) administration interferes with immune response in infants. STUDY DESIGN: A total of 1111 Filipino infants recruited into an immunogenicity and carriage study, nested in an efficacy trial, received PCV-11 or saline solution placebo at 6, 10, and 14 weeks of age. Antibody concentrations to the most frequently carried vaccine serotypes 6B, 19F, and 23F were measured by enzyme immunoassay from sera obtained at 18 weeks and 9 months of age. Serotype-specific antibody concentration was compared between groups of children among PCV-11 recipients stratified according to their carriage status at 6 weeks of age. RESULTS: Antibody concentrations to 6B, 19F, and 23F were significantly lower at 18 weeks and 9 months of age among children who were carriers of the specific serotype at 6 weeks of age than among non-carriers of the serotype. The hyporesponsiveness was specific to the carried serotype. The specific antibody concentrations induced by PCV-11 among carriers did not differ significantly from those in placebo recipients, whereas the differences were highly significant among noncarriers. CONCLUSIONS: Pneumococcal carriage, prevalent in Filipino infants, interferes with serotype-specific immune response to primary series of PCV and has potential implications for immunization programs.

Passive protection in the infant rat protection assay by sera taken before and after vaccination of teenagers with serogroup B meningococcal outer membrane vesicle vaccines.

From a previous published clinical trial among teenagers in Iceland [Perkins BA, Jonsdottir K, Briem H, Griffiths E, Plikaytis BD, Høiby EA, et al. J Infect Dis 1998;177:683--91], we evaluated a 25% stratified subset of sera, collected before vaccination and 6 weeks after the second vaccination with either the Norwegian (n=37) or the Cuban (n=35) serogroup B meningococcal outer membrane vesicle (OMV) vaccine or the control serogroup A/C capsular polysaccharide vaccine (n=20), for protective activity in an infant rat protection assay (IRPA). Protection was assessed with both the Norwegian (44/76-SL, B:15:P1.7,16:L3,7) and the Cuban (Cu 385, B:4:P1.19,15:L3,7) vaccine strain, and the results compared with serum bactericidal assay (SBA) titres and anti-OMV IgG antibody concentrations. An IRPA response was defined as a >or=10-fold rise in protective activity compared to pre-vaccination level. Forty-six percent (42/92) of the pre-vaccination sera showed protection with strain 44/76-SL compared to only 12% (11/92) with strain Cu 385. After the second dose, 22% (8/37) of those given the Norwegian vaccine showed IRPA responses with the homologous strain compared to 65% (24/37) in SBA. The corresponding numbers with the homologous strain for the Cuban vaccinees were 14% (5/35) and 29% (10/35), respectively. Among the controls, 15% (3/20) showed IRPA responses to 44/76-SL but none to Cu 385. Correlation between IRPA activity and SBA titres or anti-OMV IgG was low, especially for pre-vaccination sera against strain 44/76-SL. We conclude that the sensitivity of IRPA described herein may not be sufficient to evaluate serogroup B OMV vaccine responses from clinical samples.

Comparison of five different vaccination schedules with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine.

OBJECTIVE: To compare seroresponses to five different vaccination schedules for Haemophilus influenzae type b (Hib)-tetanus toxoid conjugate (PRP-T) vaccine in infants. DESIGN: Four different two-dose schedules were compared, with doses given at 1 and 3 months, 2 and 4 months, 2 and 6 months, or 4 and 6 months of age. One group received three doses at 2, 4, and 6 months of age. The PRP-T vaccine was given in the same syringe with diphtheria-tetanus-pertussis (DTP) vaccine; inactivated polio vaccine (IPV) was given in a separate syringe. Anti-Hib polysaccharide antibodies were measured by radioimmunoassay in sera taken before each immunization, 1 month after the second dose, at 7 and at 12 to 24 months of age. SUBJECTS: A total of 196 healthy infants were enrolled between November 1990 and November 1992. RESULTS: After one dose of PRP-T there were no significant differences in geometric mean antibody concentrations (0.09 to 0.13 microgram/ml) or in fold responses among the schedules. The response to the second dose was significantly higher than the response to the first dose given at the same age. The geometric mean antibody concentration was lower in the group vaccinated at 1 and 3 months than in the groups vaccinated at 2 and 4 months, 2 and 6 months, or 4 and 6 months. The three-dose schedule resulted in a significantly higher final antibody concentration than the best two-dose schedule (p <0.001). In most children (64% to 93%), the antibody concentration remained at least 0.15 microgram/ml up to the age of 12 to 24 months. CONCLUSIONS: The Hib conjugate vaccine, PRP-T, administered concomitantly with DTP vaccine and IPV, was immunogenic with schedules starting at 1 to 4 months of age. Two injections of PRP-T vaccine were immunogenic enough to maintain protection up to 12 to 18 months of age.

Risk factors of invasive Haemophilus influenzae type b disease among children in Finland.

A population-based matched case-control analysis of risk factors of invasive Haemophilus influenzae type b (Hib) disease was conducted in Finland in 1985 and 1986 before large-scale Hib vaccinations; 117 consecutive child patients with invasive Hib disease and 225 control subjects matched for age, sex, and residence were studied. In the multivariate analysis, day care outside the home was found to increase the risk of invasive Hib disease (odds ratio 5, 95% confidence interval 2.3 to 11), with the highest risk among children less than 2 years of age; this risk was significantly higher within the first month of attendance than later on (p = 0.02). The existence of siblings less than 7 years of age was found to be a risk factor, especially for the younger children (odds ratio 8.6, 95% confidence interval 2.6 to 52 for children less than 1 year of age), and the odds ratio increased approximately twofold with each additional sibling. A history of otitis media and previous hospitalizations were further risk factors for invasive Hib disease (odds ratio 2.2, 95% confidence interval 1.2 to 3.9, and odds ratio 1.9, 95% confidence interval 1.0 to 3.4, respectively). Breast-feeding for longer than 6 months was found to be protective (odds ratio 0.47, 95% confidence interval 0.3 to 0.9). The amount of Hib disease in different populations will vary with the incidence of these risk factors.

Meningococcus group A vaccine in children three months to five years of age. Adverse reactions and immunogenicity related to endotoxin content and molecular weight of the polysaccharide.

Vaccination of 21,007 children between the ages of three months and five years was completed with five different lots of the meningococcal group A capsular polysaccharide vaccine. A correlation was found between the frequency and severity of adverse reactions and the endotoxin content of the vaccine lots. All vaccine lots elicited a serum antibody response. The endotoxin content of the vaccines did not correlate with the serum antibody response.