Past Vaccine Studies
Cholera is an acute diarrheal illness whose symptoms include diarrhea, vomiting, and dehydration, caused by ingesting contaminated food and water. Annually, there are an estimated 100,000 deaths and 3-5 million cases worldwide, although most cases are asymptomatic or mild. Cholera is a disease of poverty, occurring most commonly in countries where access to proper water sanitation is limited. Cholera in the United States is rare, though travelers to endemic areas are at risk if they consume contaminated food or water. Often, cholera cases can be treated with oral rehydration, but more severe cases require intravenous fluid replacement and antibiotics, and untreated cholera can cause death. There is currently no vaccine available for individuals from the United States traveling to areas where cholera is present and there is no single dose cholera vaccine available for us in epidemics in endemic areas.
The University of Vermont Vaccine Testing Center (UVM VTC) conducted a clinical trial of a single-dose, oral vaccine against cholera. It is planned to first license this vaccine in the United States for use with travelers and subsequently licensed for local use in cholera-endemic countries and in the case of an outbreak.
Campylobacter jejuni infections
Campylobacter jejuni is a top cause of food-borne disease in the United States and a common cause of diarrhea in young children globally. It is uniquely associated with post-infectious sequelae, including reactive arthritis, irritable bowel syndrome and, via molecular-mimicry, ascending paralysis (the Guillain-Barré syndrome). Out lab is working to improve serodiagnostic tests for the detection of Campylobacter jejuni infections and to better understand the cellular immune responses to this infection.
Cryptosporidium is an intestinal protozoan infection which causes diarrhea, particularly in young children and immunocompromised individuals (such as persons with Acquired Immunodeficiency Syndrome, AIDS). In developing regions of the world, Cryptosporidium infection is associated with childhood malnutrition, including loss of linear growth/stunting of height. Our laboratory work has focused on how the immune response of young children to this infection contributes to the vicious cycle of diarrhea, infectious diseases and malnutrition.
We have studied the role of host genetic susceptibility and HLA alleles to Cryptosporidium infection. This work was performed as part of a field trial cohort of children in Bangladesh, in collaboration with colleagues at the University of Virginia and the ICDDRB (Dhaka, Bangladesh,http://www.icddrb.org/). Current work is examining the role of mannose-binding lectin genotypes and susceptibility to Cryptosporidium, as well as E. histolytica infections. We are also interested in determining the contribution of the human intestine T-lymphocyte populations to intestinal inflammation, as well as age-dependent changes in the host immune response to intestinal protozoa.
Salmonella typhi is a gram-negative bacterium that causes a severe febrile illness and is spread through contaminated food and water. The infection spreads in the host via invasion of host macrophages, using a type-III secretion system (TTSS). Despite the presence of vaccines against typhoid fever used for more than 100 years, typhoid fever still infects 15-30 million persons annually, killing 600,000. While the clinical arm of the VTC has been working with biotech partners to develop new typhoid vaccines, the laboratory is focused on understanding correlates of immune protection to S. typhi infection and evaluating the functional immunology of candidate vaccines.