| Abstract |
Cryptosporidium is an apicomplexan parasite that causes severe, protracted diarrhea in immunocompromised hosts, such as AIDS patients worldwide. There is no specific effective treatment for cryptosporidiosis in these patients and there is no vaccine available. The long term objective of this study is to develop interventional and preventive strategies for cryptosporidiosis in patients with HIV/AIDS. The goal of this pilot project is to investigate the immune response to specific antigens in Cryptosporidium spp. infections in HIV-infected adults in south India. Cryptosporidiosis is a major opportunistic infection in AIDS patients in India. In preliminary studies at Christian Medical College (CMC), Vellore, ~25% of HIV-infected adults with diarrhea had cryptosporidiosis, whereas ~5% of HIV-infected patients had asymptomatic cryptosporidiosis. Cryptosporidium antigens gp15 and Cp23 are conserved, immunodominant antigens which induce protective immune responses in animal models and immunocompetent human volunteers and are putative vaccine candidates. However, immune responses to these antigens in immunodeficient humans have not been characterized. Knowledge of whether immunodeficient individuals are capable of mounting immune responses to these antigens is essential for development of potential immune-based intervention strategies. The hypothesis is that immune responses to gp15 and Cp23 antigens are associated with protection from symptomatic cryptosporidiosis in HIV infected adults.
The specific aim is to investigate humoral and cell-mediated immune responses to gp15 and Cp23 in 26 HIV infected adults with symptomatic cryptosporidiosis and 26 HIV-infected adults with asymptomatic cryptosporidiosis in Vellore, South India. In Aim1a we will compare serum IgG and fecal IgA levels to gp15 and Cp23 in both groups of patients. In Aim 1b we will compare IFN? mediated cellular immune responses to these antigens in both groups and in Aim1c we will explore the relationship between immune responses to these antigens and CD4 counts in symptomatic and asymptomatic patients. This study will be carried out at CMC, Vellore. Patients will be recruited from the Infectious Disease Clinic. Laboratory investigations will be conducted in the Microbiology laboratory of the Department of Gastrointestinal Sciences at CMC. Dr.Ajjampur, a junior investigator at CMC and Adjunct Assistant Professor in the Department of Public Health at Tufts will be the Principal Investigator. Dr. Ward, Tufts-New England Medical Center will serve as mentor, and Drs. Kang and Abraham will be co-investigators at CMC and Dr. Wanke will be a co-investigator at Tufts.
There are currently no funds available for this study. If funded, results from this pilot project study will permit characterization of humoral and cell mediated immune responses to specific Cryptosporidium antigens in HIV infected patients in a developing country setting where diarrhea is known to be an important cause of morbidity and mortality in these patients. The results from this study will inform future RO1-type longitudinal studies on immune responses to specific antigens in HIV-infected patients, facilitate identification of the correlates of protective immunity, if any, in these individuals and form the basis for studies on potential immune-based interventions such as vaccines.
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