Protective Monoclonal Antibody Defines a Circumsporozoite-Like Glycoprotein Exoantigen of Cryptosporidium parvum Sporozoites and Merozoites

Michael W. Riggs, Alice L. Stone, Phaedra A. Yount, Rebecca C. Langer, Michael J. Arrowood, David L. Bentley

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

The apicomplexan protozoan parasite Cryptosporidium parvum causes a diarrheal disease in human and other mammals for which specific therapy and immunoprophylaxis are unavailable. Passive immunization with Abs against whole C. Parvum organisms has variable efficacy in immunocompromised or neonatal hosts. Because apical and surface-exposed zoite Ags of the Apicomplexa are critical to infectivity and targets of protective immunity, we examined the ability of mAbs generated against such Ags in C. parvum sporozoites to passively protect against infection and identify biologically relevant parasite molecules. A panel of mAbs was produced against affinity-purified native Ags using sporozoite apical- and surface-reactive mAb C4A1 as binding ligand. One resulting mAb, designated 3E2, elicited prominent morphologic changes in sporozoites and merozoites characterized by rapid and progressive formation, posterior movement, and release of membranous Ag-mAb precipitates. These changes has a striking resemblance to the malarial circumsporozoite precipitate (CSP) reaction. Sporozoite infectivity was completely neutralized after in vitro exposure to 3E2 and the CSP-like reaction. Furthermore, orally administered 3E2 completely prevented or markedly reduced infection in neonatal BALB/c mice. 3E2 bound to apical complex and surface molecules of zoites and was demonstrated in membranous precipitates by immunoelectron microscopy. In Western blots, 3E2 recognized multiple 46 to ∼770 kDa sporozoited Ags and an ∼1300-kDa Ag designated CSL, also expressed by merozoites. CSL was characterized as a soluble glycoprotein exoantigen released by infectious sporozoites. Further, CSL was determined to be the molecular species mechanistically involved in the CSP-like reaction by its identification in SDS-PAGE gels and Western blots of purified membranous precipitates. These findings indicate the CSL has a functional role in sporozoite infectivity and is a candidate molecular target for passive or active immunization against cryptosporidiosis.

Original languageEnglish (US)
Pages (from-to)1787-1795
Number of pages9
JournalJournal of Immunology
Volume158
Issue number4
StatePublished - Feb 15 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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