Cryptosporidium is a sporozoan parasite which replicates in the surface epithelium of the gastrointestinal and/or respiratory tract of man and other animals. Infection of immunocompetent patients results in self-limiting gastrointestinal influenza-like symptoms, but severe longstanding and life-threatening diarrhea is observed in immunodeficient patients, including those with the acquired immunodeficiency syndrome (AIDS). The severity of disease in AIDS patients is explained by two factors: 1) inability to terminate infection because of suppressed immune responsiveness and absence of effective chemotherapeutic agents, and 2) the autoinfective nature of the life cycle of Cryptosporidium, allowing merozoites and sporozoites to infect additional cells and perpetuate disease even though the patients is not re-exposed to an exogenous source of the organism. These problems could be circumvented and the disease controlled if patients received antibodies with neutralizing activity for merozoites and sporozoites of Cryptosporidium. Our research will test the hypothesis that cryptosporidiosis can be prevented and treated by administration of neutralizing antibodies reactive with infective stages of the organism. This will be accomplished by pursuing the following specific aims. 1: Produce neutralizing antibodies reactive with surface antigens of Cryptosporidium sporozoites. 2: Test sporozoite neutralizing antibodies for ability to protect against challenge by Cryptosporidium oocysts. 3: Produce neutralizing antibodies reactive with surface antigens of Cryptosporidium merozoites. 4: Test neutralizing antibodies, reactive with sporozoites and merozoites, for ability to terminate existing Cryptosporidium infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI025731-01
Application #
3139278
Study Section
(SRC)
Project Start
1987-09-30
Project End
1990-08-31
Budget Start
1987-09-30
Budget End
1988-08-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Washington State University
Department
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
Perryman, L E; Jasmer, D P; Riggs, M W et al. (1996) A cloned gene of Cryptosporidium parvum encodes neutralization-sensitive epitopes. Mol Biochem Parasitol 80:137-47
Tatalick, L M; Perryman, L E (1995) Effect of surface antigen-1 (SA-1) immune lymphocyte subsets and naive cell subsets in protecting scid mice from initial and persistent infection with Cryptosporidium parvum. Vet Immunol Immunopathol 47:43-55
Chrisp, C E; Mason, P; Perryman, L E (1995) Comparison of Cryptosporidium parvum and Cryptosporidium wrairi by reactivity with monoclonal antibodies and ability to infect severe combined immunodeficient mice. Infect Immun 63:360-2
Tatalick, L M; Perryman, L E (1995) Attempts to protect severe combined immunodeficient (scid) mice with antibody enriched for reactivity to Cryptosporidium parvum surface antigen-1. Vet Parasitol 58:281-90
Perryman, L E; Mason, P H; Chrisp, C E (1994) Effect of spleen cell populations on resolution of Cryptosporidium parvum infection in SCID mice. Infect Immun 62:1474-7
Aguirre, S A; Mason, P H; Perryman, L E (1994) Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to Cryptosporidium parvum infection. Infect Immun 62:697-9
Perryman, L E; Kegerris, K A; Mason, P H (1993) Effect of orally administered monoclonal antibody on persistent Cryptosporidium parvum infection in scid mice. Infect Immun 61:4906-8
Uhl, E W; O'Connor, R M; Perryman, L E et al. (1992) Neutralization-sensitive epitopes are conserved among geographically diverse isolates of Cryptosporidium parvum. Infect Immun 60:1703-6
Bjorneby, J M; Hunsaker, B D; Riggs, M W et al. (1991) Monoclonal antibody immunotherapy in nude mice persistently infected with Cryptosporidium parvum. Infect Immun 59:1172-6
Bjorneby, J M; Leach, D R; Perryman, L E (1991) Persistent cryptosporidiosis in horses with severe combined immunodeficiency. Infect Immun 59:3823-6

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