Immunotherapy of cryptosporidiosis in immunodeficient animal models.
Abstract: Immunotherapy for persistent infection caused by Cryptosporidium parvum was attempted in two immunodeficient animal models. BALB/c Athymic (nude) mice were infected with two oral doses of 2 x 10(7) C. parvum oocysts, and subsequently treated with monoclonal antibody (MAb) 17.41 that neutralizes sporozoites and merozoites. Persistent infection was established in all exposed mice. Daily oral treatment with MAb 17.41 for 10 days significantly reduced (p less than 0.005) the number of C. parvum organisms observed by microscopic study of intestinal tracts of infected mice. Young horses with severe combined immunodeficiency (SCID) also developed persistent infection following oral exposure with 10(8) C. parvum oocysts. In contrast to nude mice, SCID foals exhibited diarrhea associated with oocyst shedding. Two foals were treated orally with MAb 18.44 and immune serum, both of which neutralized C. parvum sporozoites and merozoites. Oocyst shedding patterns did not significantly differ from those in five SCID foals treated with nonimmune reagents. The results obtained indicate that SCID foals are a useful large animal model of clinical disease associated with persistent C. parvum infection, and that nude mice are a convenient animal model for testing therapeutic potential of antibodies in persistent cryptosporidial infection.
Publication Date: 1991-11-01 PubMed ID: 1818225
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The researchers conducted a study on immunotherapy as a treatment method for a persistent infection caused by Cryptosporidium parvum using two immunodeficient animal models: BALB/c Athymic mice and SCID foals. The results indicated a substantial reduction in the number of C. parvum organisms in mice and highlighted the potential of SCID foals as a large animal research model for persistent C. parvum infection.
Animal Models Used
- The immunodeficient animal models used were BALB/c Athymic (nude) mice and young horses with severe combined immunodeficiency (SCID), both susceptible to persistent infection after exposure to C. parvum oocysts.
- The mice were orally infected with two doses of 2 x 10^7 C. parvum oocysts and the foals were exposed orally to 10^8 oocysts, establishing persistent infection in both species.
Immunotherapy Treatment
- To treat the infected mice, they used monoclonal antibody (MAb) 17.41, which neutralizes sporozoites and merozoites of the Cryptosporidium species.
- The MAb 17.41 was administered orally to the mice for 10 consecutive days. This therapy resulted in a significant reduction (p less than 0.005) in the number of C. parvum organisms as observed through microscopic examination of the mice’s intestinal tracts.
- In comparison, SCID foals exhibited symptoms such as diarrhea and oocyst shedding. Two of the foals were treated orally with monoclonal antibody (MAb) 18.44 and immune serum, both capable of neutralizing C. parvum sporozoites and merozoites.
Results and Implications
- Despite the treatment in SCID foals, the oocyst shedding patterns did not show any significant difference compared to five SCID foals treated with nonimmune reagents. This implies that the used therapy didn’t demonstrably affect oocyst shedding in SCID foals.
- The results verify that SCID foals are a worthwhile large animal model for the study of diseases related to persistent C. parvum infections.
- The Athymic nude mice proved to be a suitable animal model for assessing the therapeutic potential of antibodies in persistent cryptosporidial infection and, due to the specific responses observed, imply potential efficacy of monoclonal antibodies in the treatment of such infections.
Cite This Article
APA
Perryman LE, Bjorneby JM.
(1991).
Immunotherapy of cryptosporidiosis in immunodeficient animal models.
J Protozool, 38(6), 98S-100S.
Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040.
MeSH Terms
- Animals
- Antibodies, Monoclonal / therapeutic use
- Antibodies, Protozoan / therapeutic use
- Cryptosporidiosis / immunology
- Cryptosporidiosis / therapy
- Disease Models, Animal
- Horses
- Immunocompromised Host
- Immunotherapy
- Mice
- Mice, Inbred BALB C
- Mice, Nude
Grant Funding
- AI 25731 / NIAID NIH HHS
Citations
This article has been cited 5 times.- Enriquez FJ, Riggs MW. Role of immunoglobulin A monoclonal antibodies against P23 in controlling murine Cryptosporidium parvum infection.. Infect Immun 1998 Sep;66(9):4469-73.
- Theodos CM, Sullivan KL, Griffiths JK, Tzipori S. Profiles of healing and nonhealing Cryptosporidium parvum infection in C57BL/6 mice with functional B and T lymphocytes: the extent of gamma interferon modulation determines the outcome of infection.. Infect Immun 1997 Nov;65(11):4761-9.
- Wyatt CR, Brackett EJ, Perryman LE, Rice-Ficht AC, Brown WC, O'Rourke KI. Activation of intestinal intraepithelial T lymphocytes in calves infected with Cryptosporidium parvum.. Infect Immun 1997 Jan;65(1):185-90.
- Perryman LE, Kegerris KA, Mason PH. Effect of orally administered monoclonal antibody on persistent Cryptosporidium parvum infection in scid mice.. Infect Immun 1993 Nov;61(11):4906-8.
- Thulin JD, Kuhlenschmidt MS, Rolsma MD, Current WL, Gelberg HB. An intestinal xenograft model for Cryptosporidium parvum infection.. Infect Immun 1994 Jan;62(1):329-31.
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