| 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 | Shannon L Harris, W James King, Wendy Ferris, Dan M Granoff
(Affiliation: Children's Hospital Oakland Research Institute, Oakland, California, USA.)
|
| Journal | Infection and immunity
(Infect Immun)
Vol. 71
Issue 1
Pg. 275-86
(Jan 2003)
ISSN: 0019-9567 United States |
| PMID | 12496177
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Antibodies, Bacterial
- Bacterial Capsules
- Meningococcal Vaccines
|
| Topics |
- Adolescent
- Adult
- Aging
(immunology)
- Animals
- Animals, Newborn
- Antibodies, Bacterial
(blood, immunology)
- Antibody Affinity
- Bacteremia
(immunology, microbiology, prevention & control)
- Bacterial Capsules
(immunology)
- Blood Bactericidal Activity
- Child
- Child, Preschool
- Disease Models, Animal
- Humans
- Immunization, Passive
- Infant
- Meningococcal Infections
(immunology, microbiology, prevention & control)
- Meningococcal Vaccines
(administration & dosage, immunology)
- Neisseria meningitidis, Serogroup C
(immunology)
- Rats
- Rats, Wistar
|
