MOUSE-HUMAN IMMUNOGLOBULIN G1 CHIMERIC ANTIBODIES WITH ACTIVITIES AGAINST CRYPTOCOCCUS-NEOFORMANS

Passive antibody administration is a potentially useful approach for t he therapy of human Cryptococcus neoformans infections. To evaluate th e efficacy of the human immunoglobulin G1 (IgG1) constant region again st C. neoformans and to construct murine antibody derivatives with red uced immunogenicities and longer half-lives in humans, two mouse-human IgG1 chimeric antibodies were generated from the protective murine mo noclonal antibodies 2D10 (IgM) and 18B7 (IgG1). The 2D10 mouse-human I gG1 chimeric antibody (ch2D10) had significantly lower binding affinit y than its parent murine antibody (m2D10), presumably because of a los s of avidity contribution on switching from IgM to IgG. The 18B7 mouse -human IgG1 chimeric antibody (ch18B7) had higher affinity for cryptoc occal polysaccharide antigen than its parent murine antibody (m18B7). ch18B7 and ch2D10 promoted phagocytosis of C. neoformans by primary hu man microglial cells and the murine J774.16 macrophage-like cell line. ch18B7 and m18B7 enhanced fungistatic or fungicidal activity of J774. 16 cells and prolonged the survival of lethally infected mice. We conc lude that the human IgG1 constant chain can be effective in mediating antifungal activity against C. neoformans. ch18B7 or similar antibodie s are potential candidates for passive antibody therapy of human crypt ococcosis.