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 \textgreater5 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 (\textgreater99\% 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 \textless 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.
%0 Journal Article
%1 harris_age-related_2003
%A Harris, Shannon L
%A King, W James
%A Ferris, Wendy
%A Granoff, Dan M
%D 2003
%J Infection and Immunity
%K Activity, Adolescent, Adult, Affinity, Aging, Animal, Animals, Antibodies, Antibody Bacteremia, Bacterial Bacterial, Bactericidal Blood C, Capsules, Child, Disease Humans, Immunization, Infant, Infections, Meningococcal Models, Neisseria Newborn, Passive, Preschool, Rats, Serogroup Vaccines, Wistar meningitidis,
%N 1
%P 275--286
%T Age-related disparity in functional activities of human group C serum anticapsular antibodies elicited by meningococcal polysaccharide vaccine
%U http://www.ncbi.nlm.nih.gov/pubmed/12496177
%V 71
%X 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 \textgreater5 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 (\textgreater99\% 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 \textless 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.
@article{harris_age-related_2003,
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 {\textgreater}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 ({\textgreater}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 {\textless} 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.},
added-at = {2011-03-11T10:05:34.000+0100},
author = {Harris, Shannon L and King, W James and Ferris, Wendy and Granoff, Dan M},
biburl = {https://www.bibsonomy.org/bibtex/24229dde55ac6a94aca57cd203b37141b/jelias},
interhash = {cf4bdbbf8284a1752e42397b7753b5fe},
intrahash = {4229dde55ac6a94aca57cd203b37141b},
issn = {0019-9567},
journal = {Infection and Immunity},
keywords = {Activity, Adolescent, Adult, Affinity, Aging, Animal, Animals, Antibodies, Antibody Bacteremia, Bacterial Bacterial, Bactericidal Blood C, Capsules, Child, Disease Humans, Immunization, Infant, Infections, Meningococcal Models, Neisseria Newborn, Passive, Preschool, Rats, Serogroup Vaccines, Wistar meningitidis,},
month = jan,
note = {{PMID:} 12496177},
number = 1,
pages = {275--286},
timestamp = {2011-03-11T10:05:37.000+0100},
title = {Age-related disparity in functional activities of human group C serum anticapsular antibodies elicited by meningococcal polysaccharide vaccine},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12496177},
volume = 71,
year = 2003
}