IMMUNOTHERAPY OF CRYPTOSPORIDIOSIS USING MONOCLONALS

Cryptosporidium parvum may produce persistent diarrheal illness in AIDS
patients. The number of infected AIDS patients is likely to be
underreported. Unfortunately, chemotherapeutic attempts at treatment have
so far failed. Recent studies have provided evidence that treatment with
hyperimmune antibody preparations may significantly reduce the severity of
disease. Following through on this idea, we plan to focus on monoclonal
antibody (Mab) approach to prophylaxis and treatment because these regent
have uniformity, can be produced in unlimited quantity, can identify
important parasite antigens and, therefore, may open up alternative
treatment strategies, and can be exhaustively tested using appropriate
animal model systems. Since it is likely that these Mabs will be most effective if a maximum
number of life cycle stages can be neutralized, we will focus on producing
neutralizing MAbs against the sporozoite merozoite and sexual stages of an
Ioqa isolate of Cryptosporidium to be provided to all program projects and
core facilities. the activity of these MAbs will be tested, either alone
or in combination, using immunocompetent neonatal mouse models of
neutralization or prophylaxis. In addition, we will test the activity of
these MAbs by using an immunocompetent neonatal mouse model of treatment
immunocompromised mouse models of prophylaxis and treatment, and by using
improved upon or newly developed in vitro cultures to study stage-specific
neutralization. Each program project will characterize and isolate
relevant stage-specific antigens and will make them available for
production of bovine-murine and human MAbs as an alternative treatment
strategy for controlling this infection in AIDS patients. Because some of
these antigens may be difficult to identify or produce, we will rely on the
construction of a cDNA and genomic library and use of appropriate library
expression vectors. Monoclonal antibodies showing prophylactic and
treatment efficacy and which warrant clinical testing eventually will be
produced in quantity.