THE EFFECT OF ELASTASE-SPECIFIC MONOCLONAL AND POLYCLONAL ANTIBODIES ON THE VIRULENCE OF ASPERGILLUS-FUMIGATUS IN IMMUNOCOMPROMISED MICE

Elastase has been implicated as a potential virulence factor involved in the invasion process of the opportunistic pathogen, Aspergillus fum igarzu. Monoclonal and polyclonal antibodies, known to inhibit elastas e in vitro, were employed in an immunocompromised mouse model of invas ive aspergillosis to determine if the antibodies could protect mice fr om fatal infection. Individual monoclonal antibodies, known to inhibit elastase partially (13 to 23%), or combinations of monoclonal antibod ies, known to inhibit elastase 70 to 100%, were tested in the mouse mo del. No individual nor combination of monoclonal antibodies protected immunosuppressed, infected mice in the doses tested. Similarly, elasta se-specific polyclonal antibodies, raised in mice or rabbits, did not exhibit a protective effect, nor did immunization of mice with elastas e prior to immunosuppression and infection. Histological examination o f the lungs of immunosuppressed, infected mice showed no amelioration of fungal invasiveness by treatment with elastase-specific monoclonal or polyclonal antibodies. However, immunocompetent mice, instilled wit h a spore inoculum much higher than used in the preceding studies and treated with antibodies, survived, while control mice not treated with antibodies were overwhelmed by the massive spore dose and died. Never theless, overall evidence suggests that elastase may not be the primar y virulence factor involved in invasive pulmonary aspergillosis.