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Infection and Immunity, November 1998, p. 5450-5456, Vol. 66, No. 11
Division of Monoclonal Antibodies, Center for
Biologics Evaluation and Research, Food and Drug Administration,
Bethesda, Maryland 20892,1 and
Division
of Biological Sciences, National Research Council of Canada,
Ottawa, Ontario, Canada K1A OR62
Received 12 May 1998/Returned for modification 21 July
1998/Accepted 24 August 1998
The polysaccharide (PS) capsules of many pathogenic bacteria are
poor immunogens in infants and young children as a result of the
delayed response to PS antigens during ontogeny. The development of
polysaccharide-protein conjugate vaccines for Haemophilus
influenzae type b, which have proven to be efficacious in this
age group, has led to active development by a number of investigators
of conjugate vaccines for other diseases. We describe here the response of several mouse strains to the capsular PS of Neisseria
meningitidis group C (MCPS) conjugated to tetanus toxoid
(MCPS-TT) and the same response in BALB/c mice as a model of the immune
consequences of conjugate vaccine immunization. The use of a conjugate
vaccine results in a shift in the isotype elicited in response to the MCPS, from immunoglobulin M (IgM) and IgG3 to primarily IgG1. A
response to MCPS-TT is seen even among mouse strains which respond poorly to MCPS itself, emphasizing the importance of a strain survey
when choosing a mouse model for a vaccine. The marked increase in IgG1
antibody titer was accompanied by a large increase in bactericidal
activity of sera from these animals. Animals primed with the conjugate
vaccine demonstrated a booster response after secondary immunization
with either the MCPS or the conjugate. The ability to produce a boosted
IgG1 anti-MCPS response to the MCPS can be transferred to adoptive
recipients by B cells alone from mice primed with MCPS-TT but not mice
primed with MCPS alone. These data indicate that in BALB/c mice a
single immunization with MCPS-TT is sufficient to induce a shift to
IgG1 and generate a memory B-cell population that does not require T
cells for boosting.
0019-9567/98/$00.00+0
Murine Immune Responses to Neisseria
meningitidis Group C Capsular Polysaccharide and a
Thymus-Dependent Toxoid Conjugate Vaccine


*
Corresponding author. Mailing address: Division of
Monoclonal Antibodies, CBER, FDA, 8800 Rockville Pike, Bethesda, MD
20892. Phone: (301) 827-0717. Fax: (301) 827-0852. E-mail:
stein{at}cber.fda.gov.
Present address: Developmental Human Vaccine Serology, Merck
Research Laboratories, West Point, PA 19486.
Present address: North American Vaccine, Inc., Beltsville, MD
20705.
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