Beth D. Kirkpatrick	Office 802 656 0016	beth.kirkpatrick@uvm.edu
	Lab 802 656 0016	110 Stafford Hall
	Infectious Disease Immunology
	Dr. Kirkpatrick received her M.D. in 1992 from Albany Medical College and completed an internship, residency and chief residency in Internal Medicine at the University of Rochester. She was a Fellow in Infectious Diseases at Johns Hopkins from 1996-1999, and joined the faculty of UVM in 1999. Dr. Kirkpatrick has been board-certified in Internal Medicine and I.D., and holds a certificate of knowledge in tropical medicine and travelers’ health.

Research Interests

Immunobiology
Microbial Pathogenesis

The overarching focus of the work in Dr. Kirkpatrick’s lab and in the Vaccine Testing Center is the concentration on Infectious Diseases of global significance.
The Kirkpatrick Lab and the Vaccine Testing Center has two main areas of interest:

Vaccine Development

Volunteers interested in details about recruitment for ongoing studies can be directed to the VTC website: Vaccine Testing Center.

Our team runs a fully functioning unit for performing phase I and II vaccine trials and enteric challenge models at the Vaccine Testing Center (VTC). In general, the VTC focuses on the development of vaccines of importance to global health, including typhoid fever, Campylobacter infections and dengue viral diseases. In 2009, the VTC began a 5-year project with Johns Hopkins University to study new Dengue and West Nile Vaccines. Other collaborators have included biotech companies, the National Institutes of Health and the Department of Defense.

Our laboratories are outfitted for scaled-up clinical immunology and microbiology work. Our staff is trained in current Good Clinical Practices (cGCP) according to FDA E9 specifications and the laboratory operates on Good Laboratory Practices-like (GLP) principles. Laboratories have the capacity for performing the immunogenicity work for multi-site vaccine trials, including specimen processing and storage. We also have the flexibility to add study-specific assays needed for vaccine trials. A detailed description of available equipment is available upon request. Experienced technicians are trained to perform validated immunologic and microbiology assays including: ELISAs, ELISPOT/ ASC/ ALS assays, functional assays of opsonization, PCR, multi-parameter flow cytometry and cell sorting, cytokine analysis (Bioplex), confocal microscopy, plaque-based assays for viral pathogens, bacterial culturing, and inoculum preparation for challenge studies.

Infectious Disease Immunology

In addition to vaccine testing, the lab is interested in characterizing how the human host responds immunologically to clinically important infectious agents and vaccines. The goal of this work is to gain a better understanding of immunologic responses to vaccines as well as natural infections.
Current projects in the lab:

1. Typhoid Fever: 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.

2. Cryptosporidium infections: 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). 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.

3. 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.

4. Dengue Virus Vaccines: Dengue virus is an RNA virus, transmitted by the Aedes egypti mosquito, which can cause a significant febrile illness (Dengue fever). Most individuals spontaneously recover from primary infection; however secondary, infections are more frequently associated severe complications, including shock and bleeding disorders. Dengue viruses cause 50-100 million infections each year, with 500,000 hospitalizations. Although most infections occur in tropical and subtropical areas, global warming has increased the risk of Dengue becoming a significant risk in areas where the disease was previously eradicated, including the United States. The development of Dengue vaccines is a priority of the National Institutes of Health. Work on dengue vaccines is a new direction for the laboratory and VTC. Over the next five years, the lab will be working with collaborators to better define cellular immune responses to live, attenuated dengue vaccines.

OPENINGS: We currently have funding for a post-doctoral fellow. Please contact Dr. Kirkpatrick for more information.

Vermont Medicine Summer 2007: The Best Defense

The Vaccine Testing Center Team, summer 2008 (missing: Nursing staff and Janet Lindow, Ph.D.)

Selected Publications

BD Kirkpatrick, Rasidul Haque, Priya Duggal, Dinesh Mondal, Cathy Larsson, Kristine Peterson, Jasmin Akter, Lauren Lockhart, Salwa Khan, William A Petri, Jr. Association of Cryptosporidium Infection with HLA Class I and II Alleles. Journal Infectious Diseases 2008; 197: 474-478.

Sears CL and Kirkpatrick BD. Is nitazoxanide an effective treatment for patients with acquired immune deficiency syndrome-related cryptosporidiosis? Nature Clinical Practice Gastroenterology & Hepatology [Commentary]. 2007; 4(3): 137.

Pierce K and Kirkpatrick BD Protozoan infections of the Gastrointestinal Tract. Current Opinion in Gastroenterology 2008; 25: 12-17.

BD Kirkpatrick, CD Huston, D Wagner, F Noel, P. Rouzier, JW Pape, G. Bois, CJ Larsson, WK Alston, K Tenney, JP O’Neill, CL Sears. Serum Mannose-binding Lectin Deficiency is Associated with Cryptosporidiosis in Young Haitian Children. Clinical Infectious Diseases. 2006; 43 (3): 289-294 [with editorial]).

Beth D. Kirkpatrick, J. Patrick O’Neill, Catherine J. Larsson, Robin McKenzie, A. Louis Bourgeois, Janet Shimko, Matthew Bentley, Jill Makin, Steve Chatfield, Zoë Hindle, Brad Robinson, Cassandra H. Ventrone, Nivedita Bansal, Colleen M. Carpenter and David N. Taylor. Evaluation of Salmonella enterica serovar Typhi ΔaroC ΔssaV, with a defined mutation in the Salmonella Pathogenicity Island 2, as a live, oral typhoid vaccine in human volunteers. Vaccine 2006; 24:116-23

All Kirkpatrick publications