Protective immunity to human cholera in Bangladesh

Diarrheal diseases are one of the most common causes of morbidity and mortality in the world today. It is estimated that a child dies of diarrhea approximately every 15-30 seconds; almost all of these deaths occur in the developing world. One of the, causative organisms, Vibrio cholerae, causes severe secretory diarrhea in humans. A prototypical mucosal infection, V. cholerae does not invade the intestinal epithelium and serves as an excellent model for the study of mucosal immunity and vaccination. The study focuses on defining the mechanisms of protective immunity to infection with V. cholerae so as to understand the requisites for the development of a protective cholera vaccine.

The central hypothesis of this proposal is that V. cholerae expresses specific proteins during early human infection, which generate immune responses that are protective on subsequent exposure; that these proteins may not be adequately expressed during colonization with currently available vaccine strains, and that these differences may explain the generally lessened efficacy of current vaccine approaches. As a result of this study, we hope to assess immune responses following cholera vaccination with the killed oral vaccines (Dukoral and/or Shanchol), and compare with responses to those seen following natural cholera. In order, to assess the duration of immunity to known cholera virulence factors, we will determine antigen-specific memory B cells circulating in human blood, to examine the longevity of B cell immunologic memory. To determine the mucosal immune responses, we will follow the immune responses using duodenal biopsies from patients recovered from cholera and correlate the duration of antigen-specific, antibody-secreting cells over a period of one year.

In addition to cholera patients, we will also study household contacts to assess innate and acquired immune responses early after exposure in household contacts of cholera patients, to determine correlates of subsequent protective immunity to cholera. The study planned is a continuation of investigations of immune responses in cholera (Pr#2005-030).

Yes, that impact the development of immune responses following cholera or that influence the development of clinical illness following exposure to the organism.