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Background. High functional antibody responses, establishment of immunologic memory, and unambiguous efficacy in infants suggest that an initial dose of conjugated pneumococcal polysaccharide (PnC) vaccine may be of value in a comprehensive adult immunization strategy. Methods. We compared the immunogenicity and safety of 7-valent PnC vaccine (7vPnC) with that of 23-valent pneumococcal polysaccharide vaccine (PPV) in adults ⩾70 years of age who had not been previously vaccinated with a pneumococcal vaccine. One year later, 7vPnC recipients received a booster dose of either 7vPnC (the 7vPnC/7vPnC group) or PPV (the 7vPnC/PPV group), and PPV recipients received a booster dose of 7vPnC (the PPV/7vPnC group). Immune responses were compared for each of the 7 serotypes common to both vaccines. Results. Antipolysaccharide enzyme-linked immunosorbent assay antibody concentrations and opsonophagocytic assay titers to the initial dose of 7vPnC were significantly greater than those to the initial dose of PPV for 6 and 5 of 7 serotypes, respectively (P<.01 and P<.05, respectively). 7vPnC/7vPnC induced antibody responses that were similar to those after the first 7vPnC inoculation, and 7vPnC/PPV induced antibody responses that were similar to or greater than antibody responses after administration of PPV alone; PPV/7vPnC induced significantly lower antibacterial responses, compared with those induced by 7vPnC alone, for all serotypes (P<.05 ). Conclusion. In adults, an initial dose of 7vPnC is likely to elicit higher and potentially more effective levels of antipneumococcal antibodies than is PPV. In contrast with PPV, for which the induction of hyporesponsiveness was observed when used as a priming dose, 7vPnC elicits an immunological state that permits subsequent administration of 7vPnC or PPV to maintain functional antipolysaccharide antibody levels. [ABSTRACT FROM AUTHOR]

When a sufficiently high proportion of a population is immunized with a vaccine, reduction in secondary transmission of disease can confer significant protection to unimmunized population members. We propose a straightforward method to estimate the degree of this indirect effect of vaccination in the context of a community-randomized vaccine trial. A conditional logistic regression model that accounts for within-randomization unit correlation over time is described, which models risk of disease as a function of community-level covariates. The approach is applied to an example data set from a pneumococcal conjugate vaccine study, with study arm and immunization levels forming the covariates of interest for the investigation of indirect effects. [ABSTRACT FROM AUTHOR]

An enzyme-linked immunoassay (EIA) is described and evaluated which quantitates human antibodies to serotype specific S. pneumoniae polysaccharide (PnPs) in human sera. Based on the observations previously described by Koskela (1), native PnPs are used as coating antigens and sera are absorbed with a soluble pneumococcal absorbant material containing C-polysaccharide (CPs) to ensure measurement of serotype specific anti-PnPs antibodies. The robustness of this method was evaluated by ten laboratories using the same reagents, protocol, and five human serum samples. Reproducible antibody values were obtained for IgM, IgG, and IgA antibodies to five different PnPs serotypes, 3, 6B, 14, 19F, and 23F. The overall mean percent coefficients of variation in this interlaboratory study for all five serotype specific anti-PnPs determinations with the five coded sera were 30% for IgG, 37% for IgM, and 36% for IgA. This assay can be standardized for quantitation of serotype specific anti-PnPs antibodies, allowing comparison of antibody values in vaccine trials evaluating pneumococcal vaccines. [ABSTRACT FROM AUTHOR]

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effect of simultaneous vitamin A supplementation and diphtheria, pertussis and tetanus (DPT) vaccination on the antibody levels. Infants aged 6-17 wk (n = 56) were randomly given 15 mg oral vitamin A or placebo at the time of their DPT immunization. Three such doses were given at monthly intervals. Immunoglobulin (Ig) G antibodies to diphtheria, pertussis and tetanus were assayed on enrollment and 1 mo after the third dose. Baseline antibody concentrations to diphtheria, pertussis and tetanus did not differ between the vitamin A-supplemented and placebo-treated groups. The postdose antibody to diphtheria level was significantly greater in the vitamin A than in the placebo-treated group. The geometric mean +/- SEM antibody levels (mg/L) were 22.9 +/- 1.2 and 11.0 +/- 1.3 in the vitamin A and placebo groups, respectively (P = 0.029). The postsupplementation concentrations of antibodies to pertussis and tetanus did not differ between the two groups. These results suggest that antibody response to diphtheria vaccination was potentiated by simultaneous vitamin A administration and DPT immunization. [ABSTRACT FROM AUTHOR]

In an attempt to develop an assay specific for antibody to capsular polysaccharide (PS) of Streptococcus pneumoniae, the ability of ELISA and Farr (radioactive antigen-binding) assay for antibodies to 6B and 19A PS to be affected by antibodies to C-polysaccharide (C-PS) was compared. Preabsorption with C-PS reduced values obtained by ELISA for anti-6B antibody by > 3-fold in 5 of 10 preimmune and 7 of 26 postimmune sera. In contrast, absorption reduced values by > 3-fold in 0 of 36 samples studied with the Farr assay. Similar results were observed when the absorption was done with CSR-SCS2 S. pneumoniae. Furthermore, when anti-19A antibody levels were examined, preabsorption with R36a S. pneumoniae reduced ELISA values by 3-fold in 7 of 22 samples, whereas no samples had 3-fold reduction by Farr assay. Thus, the Farr assay for capsular PS is less affected than the ELISA by anti-C-PS antibody. [ABSTRACT FROM AUTHOR]

Passive transfer of antibody to infants born to women immunized during the third trimester of pregnancy with a Haemophilus influenzae type b (Hib) vaccine (PRP polysaccharide or Hib conjugates PRP-D or HbOC) was studied in 50 mothers and infants and 47 nonimmunized mother-infant pairs. Geometric mean total PRP antibody by RIA was 1.2 micrograms/mL at delivery in unimmunized women and 21, 149, and 171 micrograms/mL in women who received PRP, PRP-D, and HbOC, respectively. Mean cord PRP antibody levels were 0.29, 3.0, 17.5, and 29.3 micrograms/mL for the corresponding groups. Postimmunization and cord PRP antibody levels were higher after maternal immunization with conjugate vaccines than with PRP vaccine (P < .01). PRP IgG1 subclass was transmitted more efficiently than IgG2 (56% vs. 35%, P < .01). The proportion of anti-PRP IgG transmitted from immunized mothers to infants correlated with time between immunization and delivery. Administration of PRP conjugate vaccines to women during pregnancy resulted in higher levels of PRP antibodies in infants than did polysaccharide or no vaccine. [ABSTRACT FROM AUTHOR]

Antibody to the capsular polysaccharide (CP) of Haemophilus influenzae b (Hib) is bactericidal, opsonic, and protective. Minimum protective levels of primarily IgG antibody to Hib CP, calculated from passive immunization studies, have been found to be approximately .06-.15 microgram/ml of serum. The human response to antigenic challenge with the Hib capsule, however, includes production of antibody to Hib CP of different isotypes whose function against Hib is unclear. In order to characterize the function of antibody to Hib CP of different isotypes, we purified human IgG, IgM, and IgA from the serum of an adult donor who had been previously immunized with purified Hib CP vaccine. The globulin preparations were greater than 99% isotypically pure, contained large quantities of anticapsular antibody, and differed in function against Hib. IgG antibody to Hib CP was bactericidal and opsonic for human polymorphonuclear leukocytes (PMNLs) in the presence of complement and protective in infant rats. IgM, although more bactericidal than IgG (P less than .01) and equally protective in rats, opsonized Hib poorly for PMNLs. IgA was not bactericidal or opsonic and did not prevent bacteremia and meningitis in rats challenged with Hib. We conclude that antibody directed against the capsule of Hib differs in antibacterial function depending on class. These data may be important to acurately estimate minimum protective levels of anticapsular antibody after vaccination or natural infection and may have implications for the manner in which the host clears Hib from the circulation. [ABSTRACT FROM AUTHOR]

From the pooled plasma of 54 adult donors immunized with Haemophilus influenzae type b capsular polysaccharide (CP), a human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) was prepared. The pharmacokinetics of antibody to H. influenzae type b CP in high-risk children was compared after BPIG and conventional immune serum globulin (ISG) were administered intramuscularly at a dose of 0.5–0.6 ml/kg. The increase in antibody level four to seven days after injection was ninefold higher with BPIG than with ISG and remained higher throughout the three-month follow-up period. The mean half-life of antibody to H. influenzae type b CP was similar after BPIG (27 days) and ISG (29 days). Antibody levels returned to baseline one to two months after ISG but remained significantly above baseline three months after BPIG (mean concentration, 385 ng/ml). Based on the assumption that 150 ng of IgG antibody to H. influenzae type b CP/ml is the minimal protective level, it is concluded that a single intramuscular dose of 0.5 ml of BPIG/kg will protect children for four months. [ABSTRACT FROM PUBLISHER]

A platelet transfusion from a blood group O donor, immunized 1 month before with Pneumovax, caused a hemolytic reaction in a blood group A recipient. Forty-five of 59 group O donors (76%) and all of nine group B donors immunized with Pneumovax had a fourfold or higher anti-A response. Half of the anti-A antibody in high titered donors was in the IgG fraction. Pneumovax contained approximately 30 micrograms of an A-like substance per dose; polyvalent pneumococcal vaccines prepared by two other manufactures contained very low and probably subimmunogenic concentrations. Several culture media prepared from animal tissues contained as antigen of similar physical, immunologic, and chemical properties, and were the most likely source of the contaminant. Manufacturing procedures have since been revised to eliminate A-like substances. [ABSTRACT FROM AUTHOR]

Abstract: Healthy adults aged ≥70 years (N =443) with no history of pneumococcal vaccination received 7- or 9-valent pneumococcal conjugate vaccine (PCV7 or PCV9) at 1× (PCV7 only), 2× (PCV7+PCV9), or 4× (2× PCV7+2× PCV9) dosage in a randomised, open-label study evaluating pneumococcal protein conjugate vaccine (PnC). Controls received 23-valent pneumococcal polysaccharide vaccine (PPV). Both geometric mean concentration enzyme-linked immunosorbent assay and opsonophagocytic activity antibody titres assessed 1 month after vaccination were significantly increased over baseline titres for all PCV7 serotypes, with a trend toward a dose-dependent immune response. Local reactions for the 4× dose, but not the 2× dose, were statistically significantly higher than for the 1× dose. No treatment-related serious adverse events occurred. [Copyright &y& Elsevier]

Pneumococci are a leading cause of severe bacterial disease in infants and children world wide. A possible means of protecting infants in the first few months of life is immunisation of the mother during pregnancy. We prospectively assessed pneumococcal immunisation of pregnant women to determine the amount of pneumococcal antibody transmitted to the infants in serum and milk and the half-life of the passively acquired antibody. Healthy pregnant women in Dhaka, Bangladesh, were randomised to receive pneumococcal or meningococcal vaccine with routine prenatal tetanus immunisation at 30-34 weeks of gestation. Serum and breast milk specimens from the mothers and sera from infants were collected up to 22 weeks of age and assayed for specific serum IgG, IgG1, and IgG2 and for milk IgA antibodies to pneumococcal serotypes 6B and 19F. 55 mothers and 56 infants were followed from birth to five months. Women who received pneumococcal vaccine had geometric mean antibody increases of 2.6 and 3.4 to types 6B and 19F, respectively. The mean infant/maternal antibody ratios were 0.56 and 0.59 (range 0.11-1.46) for these serotypes. Infant cord antibody titres correlated with maternal titres. Infant/maternal IgG ratios correlated with the interval between immunisation and birth and were higher for specific IgG1 than for IgG2. Infants of pneumococcal vaccine recipients had geometric mean antibody concentrations of 6.8 and 7.5 micrograms/mL to serotypes 6B and 19F in cord blood; in cord blood and in all subsequent serum specimens the concentrations were 2-3 fold higher than in control infants. The median half-life of passive antibody was about 35 days; at five months of age 63-71% of infants of pneumococcal vaccine recipients had antibody concentrations greater than 0.15 micrograms/mL. Breast milk IgA antibodies for pneumococcal serotype 19F, but not for type 6B, were significantly higher in vaccine recipients up to five months after delivery. If maternal pneumococcal polysaccharide antibodies do not interfere with active immunisation of the infant with new glycoprotein conjugate pneumococcal vaccines, passive-active immunisation of infants can be a feasible strategy for developing regions. [ABSTRACT FROM AUTHOR]