There is a need for systems to rapidly identify markers of protective immunity against a number of category A, B and C agents of high public and international health importance. In addition, there is a need for the development of platforms to rapidly evaluate the breadth and duration of immune responses following vaccination against such pathogens, correlating responses to those found to be protective. Vibrio cholerae is a category B agent, and the cause of cholera, a secretary diarrhea that results in significant morbidity and mortality worldwide. The mediators of protective immunity against cholera are poorly understood, and although a number of cholera vaccines have been developed, each has significant limitations. We propose to use previously created reagents (already-collected clinical specimens and already-produced V. cholerae NAPPA protein microarrays) to perform high throughput proteomics-based screening to identify markers of protective immunity against cholera, and to compare immune responses correlating with protection with those induced following vaccination. To do this, we propose a cooperative research partnership between researchers at the Massachusetts General Hospital (MGH), Harvard Institute of Proteomics (HIP), and International Centre for Diarrheal Disease Research in Dhaka, Bangladesh (ICDDR,B).
Specific Aim #1. Use NAPPA to screen serum of household contacts of cholera index patients, stratifying responses by level of protection from cholera. Purify antigens of interest, and confirm immune responses.
Specific Aim #2. Use NAPPA to screen antibody-in-lymphocyte supernatants of memory B cells of household contacts of cholera index patients, stratifying responses by level of protection from cholera. Purify antigens of interest, and confirm immune responses.
Specific Aim #3. Use NAPPA to screen serum of vaccines who have received killed oral whole cell cholera vaccine (WC-rBS) or live oral attenuated cholera vaccine Peru-15, comparing immunoproteomic responses to those correlating with protection from cholera. The major objective of this project is to identify and purify V. cholerae immunogens against which immunoreactivity in humans corresponds with protection from cholera. These immunogens would subsequently be evaluated for inclusion in subunit cholera vaccines or boosters.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAI1-TP-M (J2))
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Hall, Robert H
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Massachusetts General Hospital
United States
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Sugimoto, Jonathan D; Koepke, Amanda A; Kenah, Eben E et al. (2014) Household Transmission of Vibrio cholerae in Bangladesh. PLoS Negl Trop Dis 8:e3314
Uddin, Taher; Aktar, Amena; Xu, Peng et al. (2014) Immune responses to O-specific polysaccharide and lipopolysaccharide of Vibrio cholerae O1 Ogawa in adult Bangladeshi recipients of an oral killed cholera vaccine and comparison to responses in patients with cholera. Am J Trop Med Hyg 90:873-81
Weil, Ana A; Begum, Yasmin; Chowdhury, Fahima et al. (2014) Bacterial shedding in household contacts of cholera patients in Dhaka, Bangladesh. Am J Trop Med Hyg 91:738-42
Leung, Daniel T; Bhuiyan, Taufiqur R; Nishat, Naoshin S et al. (2014) Circulating mucosal associated invariant T cells are activated in Vibrio cholerae O1 infection and associated with lipopolysaccharide antibody responses. PLoS Negl Trop Dis 8:e3076
Alam, Mohammad Murshid; Bufano, Megan Kelly; Xu, Peng et al. (2014) Evaluation in mice of a conjugate vaccine for cholera made from Vibrio cholerae O1 (Ogawa) O-specific polysaccharide. PLoS Negl Trop Dis 8:e2683
Leung, Daniel T; Das, Sumon K; Malek, M A et al. (2014) Impact of Ramadan on clinical and microbiologic parameters of patients seen at a diarrheal hospital in urban Dhaka, Bangladesh, 1996-2012. Am J Trop Med Hyg 90:294-8
Bhuiyan, Saruar; Sayeed, Abu; Khanam, Farhana et al. (2014) Cellular and cytokine responses to Salmonella enterica serotype Typhi proteins in patients with typhoid fever in Bangladesh. Am J Trop Med Hyg 90:1024-30
Charles, Richelle C; Liang, Li; Khanam, Farhana et al. (2014) Immunoproteomic analysis of antibody in lymphocyte supernatant in patients with typhoid fever in Bangladesh. Clin Vaccine Immunol 21:280-5
Alam, Mohammad Murshid; Aktar, Amena; Afrin, Sadia et al. (2014) Antigen-specific memory B-cell responses to enterotoxigenic Escherichia coli infection in Bangladeshi adults. PLoS Negl Trop Dis 8:e2822
Charles, Richelle C; Hilaire, Isabelle J; Mayo-Smith, Leslie M et al. (2014) Immunogenicity of a killed bivalent (O1 and O139) whole cell oral cholera vaccine, Shanchol, in Haiti. PLoS Negl Trop Dis 8:e2828

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