Efficacy of monoclonal antibodies against defined antigens for passive immunotherapy of chronic gastrointestinal cryptosporidiosis

Cryptosporidium parvum is an important cause of diarrhea in humans and calves and can persistently infect immunocompromised hosts. Presently, there are no consistently effective parasite-specific drugs for cryptosporidiosis. We hypothesized that neutralizing monoclonal antibodies (MAbs) targeting the apical complex and surface antigens CSL, GP25-200, and P23 could passively immunize against cryptosporidiosis. We recently reported that a formulation of MAbs 3E2 (anti-CSL), 3H2 (anti-GP25-200), and 1E10 (anti-P23) provided significant additive prophylactic efficacy over that of the individual MAbs in neonatal ICR mice. In the present study, these MAbs were evaluated for therapeutic efficacy against persistent infection in adult gamma interferon-depleted SCID mice. 3E2 demonstrated the most significant and consistent therapeutic effect, reducing intestinal infection in two experiments. In one experiment, 3E2 plus 3112 and 3E2 plus 3112 plus 1E10 also significantly reduced infection; however, no significant increase in efficacy over 3E2 alone was apparent. The results indicate that anti-CSL MAb 3E2 has highly significant efficacy in reducing, but not eliminating, persistent C. parvum infection.