181184 Memory B cell responses in patients with dehydrating diarrhea caused by Vibrio cholerae O1

Tuesday, October 28, 2008

Aaron Michael Harris, BA , Department of Family Medicine and Public Health, Tufts University School of Medicine, Boston, MA
Md. Saruar Bhuiyan, MS , Laboratory of Immunology, International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh
Azim Hossain, MS , Laboratory of Immunology, International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh
Jason B. Harris, MD , Department of Medicine, Harvard Medical School, Boston, MA
Fahima Chowdhury, MD , Laboratory of Immunology, International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh
Ashraful I. Khan, MD , Laboratory of Immunology, International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh
Regina C. LaRocque, MD , Department of Medicine, Harvard Medical School, Boston, MA
Ed T. Ryan, MD , Department of Medicine, Harvard Medical School, Boston, MA
Firdausi Qadri, PhD , Laboratory of Immunology, International Center for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh
Stephen Calderwood, MD , Department of Medicine, Harvard Medical School, Boston, MA
Purpose:

Cholera, caused by Vibrio cholerae, is a non invasive enteric disease with a high mortality rate if untreated. Transmission of this disease is fecal-oral, most commonly when a host ingests water that has been contaminated by sewage. Developing countries, such as Bangladesh, suffer from cholera epidemics as a result of inadequate water supplies and access to clean drinking water. A more effective vaccine to prevent cholera is needed.

Explain the data or information used:

We performed a prospective cohort study of patients with cholera followed for one year. The objective was to quantitate antigen specific memory B-lymphocytes in the peripheral circulation that might be responsible for protective immunity to cholera.

Methods:

We enrolled 30 culture confirmed cholera infected patients and followed them at time of infection, days 30, 90, 180, 270, and 360. We detected immune responses using a method of polyclonal stimulation of peripheral blood mononuclear cells followed by a double-color ELISPOT procedure for development of cholera toxin B subunit (CTB), lipopolysaccharide (LPS), and toxin-coregulated pilus A (TcpA) specific IgG and IgA memory B-lymphocyte responses.

Major results:

All patients demonstrated CTB, TcpA, and LPS-specific IgG and IgA memory responses by day 90, which persisted up to one year, substantially longer than other immunologic markers following cholera, including the serum vibriocidal response and serum IgG or IgA to these antigens.

Recommendations:

This study suggests that long term immunity to cholera may be mediated by antigen specific memory B-lymphocytes; further analysis of these responses in protection from cholera is ongoing.

Learning Objectives:
1. List antigens that induce a memory B cell response in patients previously infected with cholera. 2. Apply immunologic methods to assess immune responses to cholera. 3. Assess possible antigen targets that could be targets for vaccine development.

Keywords: Diarrhea, Immunizations

Presenting author's disclosure statement:

Qualified on the content I am responsible for because: I have no conflicts of interest.
Any relevant financial relationships? No

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.