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 micro g 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 (> or =2-log(10) reduction compared to control animals) the level of
bacteremia following a challenge. Of 79 neonate rats that received > or =0.031 micro g of human infant anti-N. meningitidis serogroup C PS
IgG, 75 (94.9%) had a > or =2-log(10) reduction in
bacteremia, whereas of the animals that received <0.031 micro g of
antigen-specific
IgG, 10.3% (4 of 39 rats) showed a > or =2-log(10) 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.