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Infection and Immunity, January 2003, p. 275-286, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.275-286.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Age-Related Disparity in Functional Activities of Human Group C Serum Anticapsular Antibodies Elicited by Meningococcal Polysaccharide Vaccine

Shannon L. Harris,1 W. James King,2 Wendy Ferris,2 and Dan M. Granoff1*

Children's Hospital Oakland Research Institute, Oakland, California,1 Department of Pediatrics, Children's Hospital Eastern Ontario, University of Ottawa, Ottawa, Canada2

Received 19 July 2002/ Returned for modification 27 August 2002/ Accepted 23 September 2002

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 ~103 CFU of either strain developed >5 x 105 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 µg/rat. Anticapsular antibody at doses fivefold higher (0.18 to 0.2 µg/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.

* Corresponding author. Mailing address: 5700 Martin Luther King Jr. Way, Oakland, CA 94609. Phone: (510) 450-7640. Fax: (510) 450-7915. E-mail: dgranoff{at}chori.org.

Editor: D. L. Burns

Infection and Immunity, January 2003, p. 275-286, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.275-286.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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