MassGeneral Hospital for Children News

Vibrio cholerae causes an estimated 5 million cases of diarrhea and over 100,000 deaths annually, predominantly in children. Although natural infection with cholera results in long-term protection against subsequent infection, the mechanisms by which this immunity is generated remain poorly understood. This is a critical problem since cholera vaccines have proven relatively ineffective, especially in children. Because of this, the development of improved cholera vaccines is considered a priority by the World Health Organization.

Immunity to Cholera

Research of Jason Harris, MD

07/May/2010

Description of research

Vibrio cholerae causes an estimated 5 million cases of diarrhea and over 100,000 deaths annually, predominantly in children. Although natural infection with cholera results in long-term protection against subsequent infection, the mechanisms by which this immunity is generated remain poorly understood. This is a critical problem since cholera vaccines have proven relatively ineffective, especially in children. Because of this, the development of improved cholera vaccines is considered a priority by the World Health Organization.

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Our research is focused on characterizing the human adaptive immune response in natural cholera, and comparing this with the immune response to cholera vaccines. This effort involves extensive collaboration through human observational studies performed at the International Center for Diarrhoeal Disease Research, Bangladesh.

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Current work in this area is focused on several facets of the immune response to natural cholera and vaccination, including: 1. identifying key features of the innate immune response, 2. characterizing the CD4+ T-cell response to selected V. cholerae antigens, 3. defining the characteristics of memory B cell responses to V. cholerae antigens and assessing their role in protective immunity against cholera, and 4. identifying host and environmental immunomodulatory factors that influence the subsequent development of adaptive immune responses to cholera. Through these studies, we hope to better understand the mechanisms of long term immunity to cholera, with the goal of laying a foundation for the design of improved cholera vaccines.

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Selected References

Harris JB, Khan AI, Larocque RC, Dorer DJ, Chowdhury F, Faruque AS, Sack DA, Ryan ET, Qadri F, Calderwood SB. Blood Group, Immunity, and Risk of Infection with Vibrio cholerae in an Area of Endemicity. Infect Immun. 2005; 73 (11): 7422-7.

Harris JB, LaRocque RC, Chowdhury F, Khan AI, Logvinenko T, Faruque ASG, Ryan ET, Qadri F, Calderwood SB. Susceptibility to Vibrio cholerae Infection in a Cohort of Household Contacts of Patients with Cholera in Bangladesh. PLoS Negl Trop Dis 2008; 2(4): 221.

Harris JB, Podolsky MJ, Bhuiyan TR Chowdhury F, Khan AI, LaRocque RC, Logvinenko T, Kendall J, Faruque AS, Ryan ET, Qadri F, Calderwood SB. Immunologic responses to Vibrio cholerae in patients co-infected with intestinal parasites in Bangladesh. PLoS Negl Trop Dis. 2009; 3 (3): e403.

Harris AM, Bhuiyan S, Chowdhury F., Khan AI, LaRocque RC, Ryan ET, Qadri F, Calderwood SB, Harris JB. Memory B cell responses to Vibrio cholerae O1 infection in Bangladesh. Infect Immun. 2009 Sep; 7 (9): 850-6.

Nelson EJ, Harris JB, Morris G, Calderwood SB, Camilli A. Cholera: The host, pathogen and bacteriophage dynamic. Nature Reviews Microbiology. 2009 Oct ; 7 (10): 693-702.

Weil AA, Chowdhury F, Khan AI, Larocque RC, Ryan ET, Calderwood SB, Qadri F, Harris JB. Clinical outcomes in household contacts of cholera patients. Clin Infect Dis. 2009 Nov 15;49(10):1473-9.

Biosketch. Dr. Harris received his M.D. from Duke University and M.P.H. from the Harvard School of Public Health. He was a pediatric resident at the MassGeneral Hospital for Children. To better understand the immune response to cholera and typhoid fever, Dr. Harris has been working in the Division of Infectious Disease at Massachusetts General Hospital and at the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh since 2003. Current funding includes career development awards from the National Institutes of Health (Fogarty International Center), the Charles H. Hood Foundation and the Philip J. Porter Fund.

 

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