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Infection and Immunity, January 2000, p. 239-246, Vol. 68, No. 1
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 21 July 1999/Accepted 20 October 1999
Antibody (Ab) responses to polysaccharides (PSs) such as
Neisseria meningitidis group C PS (MCPS) are characterized
as being thymus independent (TI) and are restricted with regard to
clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled to tetanus toxoid (MCPS-TT), elicits a thymus-dependent (TD)
response. In order to understand the influence of the form of a vaccine
(TI versus TD) on the Ab repertoire, we generated monoclonal antibody
(MAb) panels from mice immunized and boosted with MCPS or MCPS-TT in
different ways. The panels of MAbs were examined for isotype, fine
specificity, affinity, and VH gene family usage. The use of
MCPS-TT resulted in a shift in the isotype from immunoglobulin M (IgM)
and IgG3 elicited in response to the MCPS to primarily IgG1. This
isotype shift was accompanied by a change in the fine specificity of
the response to the conjugate compared to that of PS. New fine
specificities and increased affinity were observed in response to the
TD antigen (Ag). Dot blot and Northern analyses of MCPS MAbs revealed
that VH gene family usage is dominated by
VHJ558, used by 23 of 39 MAbs. VH3609 was seen in three MAbs of restricted fine specificity. VHQ52,
VH7183, and VHVGAM3-8 were seen in more than
one MAb across these panels, while VH10 and
VHX24 were detected only once in response to the TI-2 Ag.
All MAbs in the panels utilized kappa light chains, and all functional
J
0019-9567/0/$04.00+0
Murine Immune Response to Neisseria
meningitidis Group C Capsular Polysaccharide: Analysis of
Monoclonal Antibodies Generated in Response to a Thymus-Independent
Antigen and a Thymus-Dependent Toxoid Conjugate Vaccine


genes were expressed.
*
Corresponding author. Mailing address: Division of
Monoclonal Antibodies, CBER, FDA, 29 Lincoln Dr., Bethesda, MD 20892. Phone: (301) 827-0850. Fax: (301) 827-0852. E-mail:
stein{at}cber.fda.gov.
Present address: Division of Vaccines and Related Products
Applications, CBER, FDA, Rockville, MD 20852.
Present address: Developmental Human Vaccine Serology, Merck
Research Laboratories, West Point, PA 19486.
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