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Infection and Immunity, November 1998, p. 5450-5456, Vol. 66, No. 11
0019-9567/98/$00.00+0

Murine Immune Responses to Neisseria meningitidis Group C Capsular Polysaccharide and a Thymus-Dependent Toxoid Conjugate Vaccine

Leonard J. Rubinstein,1,dagger Pablo A. García-Ojeda,1 Francis Michon,2,Dagger Harold J. Jennings,2 and Kathryn E. Stein1,*

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.

* 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.

dagger Present address: Developmental Human Vaccine Serology, Merck Research Laboratories, West Point, PA 19486.

Dagger Present address: North American Vaccine, Inc., Beltsville, MD 20705.

Infection and Immunity, November 1998, p. 5450-5456, Vol. 66, No. 11
0019-9567/98/$00.00+0


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