A glycoconjugate vaccine for Neisseria meningitidis induces antibodies in human infants that afford protection against meningococcal bacteremia in a neonate rat challenge model.
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.
Mountzouros
Kenneth T
KT
Wyeth Research, West Henrietta, New York 14586-9728, USA. mountzk@wyeth.com
Belanger
Kelly A
KA
Howell
Alan P
AP
Bixler
Garvin S
GS
Madore
Dace V
DV
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D001770:Blood Bactericidal Activity; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D007231:Infant, Newborn; D008589:Meningococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
D000907:Antibodies, Bacterial; D003176:Complement C3; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate