Anticapsular serum antibody concentration and protection against pneumococcal colonization among children vaccinated with 7-valent pneumococcal conjugate vaccine.

BACKGROUND: Pneumococcal conjugate vaccines prevent invasive and noninvasive disease due to infection with vaccine serotypes. Pneumococcal conjugate vaccines also prevent nasopharyngeal acquisition of vaccine serotypes, although the mechanism is incompletely understood. METHODS: An efficacy trial of a 7-valent pneumococcal conjugate vaccine was conducted on the Navajo and White Mountain Apache reservations, located in the Southwestern United States; group C meningococcal conjugate vaccine was the control vaccine. Infants were randomized to receive 7-valent pneumococcal conjugate vaccine or group C meningococcal conjugate vaccine at 2, 4, 6, and 12 months of age. Immunogenicity and nasopharyngeal colonization studies were nested in the efficacy trial. We analyzed the correlation between serotype-specific serum IgG concentration at 7 and 13 months of age and nasopharyngeal acquisition of disease at 12 and 18 months of age, respectively. We adjusted for potential confounders using multivariate logistic regression. RESULTS: Among 203 subjects, we observed 60 acquisitions of vaccine-type pneumococci, including 19 acquisitions of serotype 19F (31.7%), and 17 acquisitions of serotype 23F (28.3%). Among recipients of 7-valent pneumococcal conjugate vaccine, increased serotype-specific serum IgG was associated with a reduction in nasopharyngeal acquisition of serotype 23F (relative risk, 0.53; 95% confidence interval, 0.31-0.93) but was not associated with a reduction in acquisition of serotype 19F (relative risk, 1.07; 95% confidence interval, 0.57-2.03). Among group C meningococcal conjugate vaccine recipients, serotype-specific serum IgG was not associated with a reduction in nasopharyngeal acquisition for either serotype. CONCLUSION: An increase in serum antibody concentration was associated with reduced acquisition of serotype 23F pneumococcus (but not with reduced acquisition of serotype 19F pneumococcus) among recipients of 7-valent pneumococcal conjugate vaccine. Differences in antibody concentration, in the functional characteristics of antibody, or in antibody kinetics during infancy may account for differences in carriage protection.

Pneumococcal conjugate vaccines: emerging clinical information and its implications.

Since 2000, when the first pneumococcal conjugate vaccine was introduced into routine use in the USA, it has had a substantial impact on invasive pneumococcal disease both in the immunized and nonimmunized population. It has also been shown to reduce pneumonia and otitis in young children and has reduced antibiotic nonsusceptible pneumococcal infections. In the USA, three primary doses and a booster dose are recommended (a so-called '3 + 1 schedule'). Some countries have or will soon introduce routine immunization with fewer doses, with either two primary doses and a booster dose ('2 + 1 schedule') or no booster dose ('3 + 0 schedule'). Some serotypes produce less antibody in a two-dose compared with a three-dose primary series. The booster dose may also be important in reducing nasopharyngeal carriage, hence absence of a booster dose may reduce indirect protection. It remains to be seen whether these schedule changes will reduce vaccine effectiveness within the population. Important future developments include extending the number of serotypes included in the vaccine and the possible extension of use into adults in whom indirect protection has been useful, but not as extensive as might be possible with direct immunization.

Transmissibility, infectivity and immunogenicity of a live human parainfluenza type 3 virus vaccine (HPIV3cp45) among susceptible infants and toddlers.

BACKGROUND: This study examined the transmissibility between young children of an intranasally administered live attenuated human parainfluenza virus type 3 (HPIV3)-cp45 vaccine candidate. METHODS: Eighty subjects were enrolled in playgroups among whom there was at least one infected vaccinee in close contact with a seronegative placebo recipient over 21 days without a confounding infection with wtHPIV3. Following vaccination viral cultures were obtained on nine occasions to detect shedding and transmission of HPIV3cp45. Serum antibody titers were measured before and 7 weeks after vaccination. RESULTS: No child fulfilled the criteria for transmission of HPIV3cp45 giving a risk of transmission of 0.04 (95% CI 0.01-0.19), hence establishing that HPIV3cp45 is less infectious than wtHPIV3 and risk of transmission is not a limitation to further clinical development of this vaccine candidate.

The interferon antagonist NS2 protein of respiratory syncytial virus is an important virulence determinant for humans.

BACKGROUND: Respiratory syncytial virus (RSV) is targeted for vaccine development, because it causes severe respiratory tract illness in the elderly, young children, and infants. A primary strategy has been to derive live attenuated viruses for use in intranasally administered vaccines that will induce a protective immune response. In the present study, the NS2 gene, whose encoded protein antagonizes the host's interferon- alpha / beta response, was deleted from RSV vaccine candidates by use of reverse genetics. METHODS: Three NS2 gene-deleted RSV vaccine candidates were studied: rA2cp Delta NS2, rA2cp248/404 Delta NS2, and rA2cp530/1009 Delta NS2. rA2cp Delta NS2, which had the fewest attenuating mutations, was evaluated in adults and RSV-seropositive children. rA2cp248/404 Delta NS2 and rA2cp530/1009 Delta NS2 were evaluated in adults and RSV-seropositive and RSV-seronegative children. RESULTS: At a high dose (10(7.0) pfu), rA2cp Delta NS2 was not shed by adults, and only 13% of them had an immune response. The other vaccine candidates, rA2cp248/404 Delta NS2 and rA2cp530/1009 Delta NS2, had greatly decreased infectivity in RSV-seronegative children, compared with that of their immediate parent strains, which possess an intact NS2 gene. CONCLUSIONS: Deletion of the NS2 gene attenuates RSV in subjects of all ages studied. This validates the strategy of developing live respiratory tract virus vaccines in which the virus's ability to inhibit the human innate immune system is blocked. rA2cp248/404 Delta NS2 should be studied in children at a higher input titer, because it was more infectious and immunogenic than was rA2cp530/1009 Delta NS2.