Abstract

Cholera is a severe dehydrating illness of humans. It is endemic in over 50 countries and causes 3 to 5 million cases a year, resulting in approximately 100,000 deaths. Currently available cholera vaccines have shortcomings. They are often poorly immunogenic in children under the age of 5 years, and often do not induce robust long-term memory responses in immunologically nave populations. We provide strong preliminary data that antibodies targeting O-specific polysaccharide (OSP) affect Vibrio cholerae and are associated with protection against cholera. We here propose an international clinical study approach to investigate the impact of OSP-specific antibodies on V. cholerae and to define OSP-specific immune responses in humans.

Public Health Relevance

Relevance to public health Currently available oral cholera vaccines have a number of shortcomings. Developing improved vaccines or vaccination strategies is hampered by the reality that we do not currently understand the mechanism of immune protection against cholera. We have strong preliminary evidence that immune responses targeting O-specific polysaccharide (OSP) affect Vibrio cholerae, and we here propose an investigative approach to define and evaluate these effects.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI106878-06A1
Application #
10116755
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Hall, Robert H
Project Start
2013-08-07
Project End
2025-03-31
Budget Start
2020-09-15
Budget End
2021-03-31
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114

  Publications

Bhuiyan, Taufiqur Rahman; Hoq, Mohammad Rubel; Nishat, Naoshin Sharmin et al. (2018) Assessing antigen specific HLA-DR+ antibody secreting cell (DR+ASC) responses in whole blood in enteric infections using an ELISPOT technique. Microbes Infect 20:122-129
Bourque, Daniel L; Bhuiyan, Taufiqur Rahman; Genereux, Diane P et al. (2018) Analysis of the Human Mucosal Response to Cholera Reveals Sustained Activation of Innate Immune Signaling Pathways. Infect Immun 86:
Domman, Daryl; Chowdhury, Fahima; Khan, Ashraful I et al. (2018) Defining endemic cholera at three levels of spatiotemporal resolution within Bangladesh. Nat Genet 50:951-955
Levade, Inès; Terrat, Yves; Leducq, Jean-Baptiste et al. (2017) Vibrio cholerae genomic diversity within and between patients. Microb Genom 3:
Xu, Peng; Kelly, Meagan; Vann, Willie F et al. (2017) Conjugate Vaccines from Bacterial Antigens by Squaric Acid Chemistry: A Closer Look. Chembiochem 18:799-815
Charles, Richelle C; Nakajima, Rie; Liang, Li et al. (2017) Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh. J Infect Dis 216:125-134
Bhuiyan, Taufiqur Rahman; Hoq, Mohammad Rubel; Nishat, Naoshin Sharmin et al. (2016) Enumeration of Gut-Homing ?7-Positive, Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients, Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique. Clin Vaccine Immunol 23:27-36
Uddin, Muhammad Ikhtear; Islam, Shahidul; Nishat, Naoshin S et al. (2016) Biomarkers of Environmental Enteropathy are Positively Associated with Immune Responses to an Oral Cholera Vaccine in Bangladeshi Children. PLoS Negl Trop Dis 10:e0005039
Hatzios, Stavroula K; Abel, Sören; Martell, Julianne et al. (2016) Chemoproteomic profiling of host and pathogen enzymes active in cholera. Nat Chem Biol 12:268-274
Iyer, Anita S; Bouhenia, Malika; Rumunu, John et al. (2016) Immune Responses to an Oral Cholera Vaccine in Internally Displaced Persons in South Sudan. Sci Rep 6:35742

Showing the most recent 10 out of 33 publications