title: Age-related disparity in functional activities of human group C serum anticapsular antibodies elicited by meningococcal polysaccharide vaccine.
abstract: Serum bactericidal activity confers protection against meningococcal disease, but it is not known whether vaccine-induced anticapsular antibodies that lack bactericidal activity are protective. We developed an infant rat challenge model using a naturally occurring O-acetylated strain of Neisseria meningitidis group C and a strain that was negative for O acetylation (OAc). Rats 4 to 7 days of age inoculated intraperitoneally (i.p.) with approximately 10(3) CFU of either strain developed >5 x 10(5) CFU/ml of blood obtained 18 h later. Dilutions of preimmunization sera given i.p. 2 h before the bacterial challenge had no effect on bacteremia, whereas group C anticapsular antibody in sera from adults immunized with meningococcal polysaccharide vaccine conferred complete or partial (>99% decrease in CFU per milliliter of blood) protection against the OAc-positive or OAc-negative strain, respectively, at antibody doses as low as 0.04 micro g/rat. Anticapsular antibody at doses fivefold higher (0.18 to 0.2 micro g/rat) in pooled sera from children immunized at a mean age of 2.6 years failed to protect rats, but antibody at the same or fivefold-lower dose in a serum pool from a group of children immunized at 4 years of age gave complete or partial protection. Protective activity was observed with some serum pools that lacked detectable complement-mediated bactericidal activity (titers < 1:4) and correlated with increasing antibody avidity. Thus, not only does the magnitude of the group C antibody response to meningococcal polysaccharide vaccine increase with increasing age but there are also age-related affects on antibody functional activity such that higher serum concentrations of vaccine-induced antibody are required for protection of immunized children than for immunized adults.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Harris
authors.forename: W James
authors.initials: WJ
authors.lastname: King
authors.forename: Wendy
authors.initials: W
authors.lastname: Ferris
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology*; D000915:Antibody Affinity; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D016667:Bacterial Capsules / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D007223:Infant; D008589:Meningococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines