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Infection and Immunity, September 2009, p. 3850-3856, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00369-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

International Centre for Diarrheal Disease Research, Bangladesh, Centre for Health and Population Research, Dhaka, Bangladesh,1 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts,2 Department of Medicine, Harvard Medical School, Boston, Massachusetts,3 Emory Vaccine Center, Emory University, Atlanta, Georgia,4 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts,5 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts,6 Department of Pediatrics, Harvard Medical School, Boston, Massachusetts7
Received 31 March 2009/ Returned for modification 7 May 2009/ Accepted 6 June 2009
Cholera, caused by Vibrio cholerae, is a noninvasive dehydrating enteric disease with a high mortality rate if untreated. Infection with V. cholerae elicits long-term protection against subsequent disease in countries where the disease is endemic. Although the mechanism of this protective immunity is unknown, it has been hypothesized that a protective mucosal response to V. cholerae infection may be mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue. To characterize memory B-cell responses to cholera, we enrolled a cohort of 39 hospitalized patients with culture-confirmed cholera and evaluated their immunologic responses at frequent intervals over the subsequent 1 year. Memory B cells to cholera antigens, including lipopolysaccharide (LPS), and the protein antigens cholera toxin B subunit (CTB) and toxin-coregulated pilus major subunit A (TcpA) were enumerated using a method of polyclonal stimulation of peripheral blood mononuclear cells followed by a standard enzyme-linked immunospot procedure. All patients demonstrated CTB, TcpA, and LPS-specific immunoglobulin G (IgG)and IgA memory responses by day 90. In addition, these memory B-cell responses persisted up to 1 year, substantially longer than other traditional immunologic markers of infection with V. cholerae. While the magnitude of the LPS-specific IgG memory B-cell response waned at 1 year, CTB- and TcpA-specific IgG memory B cells remained significantly elevated at 1 year after infection, suggesting that T-cell help may result in a more durable memory B-cell response to V. cholerae protein antigens. Such memory B cells could mediate anamnestic responses on reexposure to V. cholerae.
Published ahead of print on 15 June 2009.
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