<i>Cryptococcus neoformans</i> infections: aspartyl protease potential to improve outcome in susceptible hosts

Vaccination and immunotherapies against fungal pathogens still remain a challenge. Here, we show using an <i>in vivo</i> model based on outbred mice that development of antibodies against Pep1p, an antigenic protein of the fungal pathogen <i>Cryptococcus neoformans</i>, confers resistance to this fungal infection. In support of this observation, prophylactic or therapeutic immunization of the mice with recombinant Pep1p could improve their survival when infected with a lethal dose of <i>C. neoformans</i>. Moreover, passive therapy with monoclonal anti-Pep1p antibodies also enhanced survival of the mice from <i>C. neoformans</i> infection. The associated antifungal mechanisms were mounting of a protective immune response and the development of fungal specific antibodies that decrease the fungal burden due to an increase in their phagocytosis and/or inhibit the fungal multiplication. Together, our study demonstrates (a) the mode of host-fungal interaction and the immune response developed thereby play a crucial role in developing resistance against <i>C. neoformans</i>; (b) Pep1p, an aspartic protease as well as an antigenic protein secreted by <i>C. neoformans</i>, can be exploited for vaccination (both prophylactic and therapeutic) or immunotherapy to improve the host defense during this fungal infection.