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.
|Rychert, Jenna; Creely, David; Mayo-Smith, Leslie M et al. (2015) Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of Vibrio cholerae. J Clin Microbiol 53:329-31|
|Chowdhury, Fahima; Mather, Alison E; Begum, Yasmin Ara et al. (2015) Vibrio cholerae Serogroup O139: Isolation from Cholera Patients and Asymptomatic Household Family Members in Bangladesh between 2013 and 2014. PLoS Negl Trop Dis 9:e0004183|
|Leung, Daniel T; Das, Sumon K; Malek, M A et al. (2015) Concurrent Pneumonia in Children Under 5 Years of Age Presenting to a Diarrheal Hospital in Dhaka, Bangladesh. Am J Trop Med Hyg 93:831-5|
|Falkard, Brie; Uddin, Taher; Rahman, M Arifur et al. (2015) Plasma Leptin Levels in Children Hospitalized with Cholera in Bangladesh. Am J Trop Med Hyg 93:244-9|
|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|
|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|
|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|
|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|
|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|
|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|
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