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Infection and Immunity, December 2002, p. 6576-6582, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6576-6582.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Glycoconjugate Vaccine for Neisseria meningitidis Induces Antibodies in Human Infants That Afford Protection against Meningococcal Bacteremia in a Neonate Rat Challenge Model

Wyeth Research, West Henrietta, New York 14586-9728

Received 10 August 2002/ Returned for modification 24 July 2002/ Accepted 28 August 2002

The functional activities of serum samples from human infants immunized with a glycoconjugate vaccine for Neisseria meningitidis serogroup C were assessed in a complement-mediated antibody-dependent serum bactericidal assay (SBA) and in a neonate rat model of protection from bacteremia. Selective serum samples from individual human infants were combined to make a panel of 11 serum pools to obtain a sufficient volume for testing. Each pool was assayed (i) for the anti-N. meningitidis serogroup C capsular polysaccharide (PS) immunoglobulin G (IgG) concentration as determined by reactivity in a direct-binding enzyme-linked immunosorbent assay, (ii) for bactericidal activity against N. meningitidis serogroup C strain C11, and (iii) for the ability to reduce bacteremia after passive transfer into a neonate rat model. Representative serum samples from infants who were not previously immunized with any N. meningitidis serogroup C vaccine served as a negative control. The prepared serum pools ranged in antibody concentration from 0.18 to 17.31 µg of IgG specific for N. meningitidis serogroup C PS per ml. For this serum panel, a direct relationship between concentrations of anti-N. meningitidis serogroup C PS-specific IgG and serum SBA titers (r = 0.9960) was observed. Passive transfer to neonate rats demonstrated the ability of postimmunization serum samples to significantly reduce (2-log₁₀ reduction compared to control animals) the level of bacteremia following a challenge. Of 79 neonate rats that received 0.031 µg of human infant anti-N. meningitidis serogroup C PS IgG, 75 (94.9%) had a 2-log₁₀ reduction in bacteremia, whereas of the animals that received <0.031 µg of antigen-specific IgG, 10.3% (4 of 39 rats) showed a 2-log₁₀ reduction in bacteremia. It was concluded that the anti-N. meningitidis serogroup C PS IgG antibody induced by this glycoconjugate vaccine had in vitro functional activity (as determined by a SBA) and also afforded protection against meningococcal bacteremia in an animal model.

Editor: A. D. O'Brien

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