This is an application for a Gammacell irradiator, containing a caesium source. It is to substitute for our current one, purchased more than 30 years ago, of which the caesium source has decayed greatly. This instrument is used several times a week by a large number of faculties of the Departments of Medical and Molecular Parasitology and Pathology, and others at NYU School of Medicine, which has the largest number of investigators working on malaria vaccine development in an Academic Institution in the U.S. In addition, several HIV investigators of the Department of Medicine at NYU School of Medicine, and Veterans Affairs use this source of irradiation. The universally recognized """"""""gold standard of protective anti-malaria immunity,"""""""" i.e. the immunization of mice with irradiated sporozoites, is a necessary control for the development of all pre-erythrocytic vaccine candidates. Currently, it takes much too long a time to attenuate sporozoites of rodent malaria (45 minutes), which meanwhile lose their infectivity and immunogenicity. Protective anti-malaria immunity will be explored by the following approaches: a) immunization with a recombinant Yellow Fever Vaccine (17D) expressing sequence of the CS protein; b) extend the duration of a NYU/Apovia vaccine candidate currently in Phase I trials; c) elucidation of the effect of human NKT cells on plasmodial liver stages, and the adjuvant activity of a-galactosylceramide in enhancing anti-malaria and anti- HIV immune responses; d) determine whether vaccination against sporozoites influences the migration of sporozoites from the skin to the blood; e) Determine the relationship of apoptotic death of hepatocytes by infection with irradiated sporozoites to the initiation of a protective anti malaria immune response mediated by dendritic cells; f) define the immune response and the respective malaria antigens operating in transgenic mice made tolerant to CS, and the immune response to immunization with early exo-erythrocytic generated in vitro in the absence of host cells; g) is an HIV related project aiming to clarify how anti-CD4+ binding antibodies interfere with gp 120 presentation.
