CIRCUMSPOROZOITE BASED MULTIPLE ANTIGEN PEPTIDES AS MALARIA VACCINE

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Over the past several years, investigators in the Department of Medical and Molecular Parasitology at the New York University School of Medicine have explored the use of multiple antigen peptides (MAPs) as the basis for vaccines against malaria. The work has focused on peptides derived from the circumsporozite protein (CSP); experimental immunogens based on the CSP of human malaria parasites have been studied for immunogenicity, while rodent malaria parasite homolog systems have enabled both immunogenicity and efficacy determinations. Sequences derived from the central repeat region of the CSP have provided to B epitopes portion of the MAPs, whereas T epitopes from several portions of the CSP have been used. MAPs have been produced which exhibit excellent immunogenicity as determined by ELISA titers against the immunogens and IFA titers against whole sporozoites. Highly immunogenic MAPs have proven to be highly protective in rodent malaria systems. One Plasmodium falcip arum MAP in particular, designated (T1B)4 has proven to be highly immunogenic. When administered with alum as adjuvant, this MAP is highly immunogenic in responder mouse strains, resulting in antibody titers orders of magnitude greater than those seen in immunization regimen is the standard used for induction of protection against malaria in a variety of host parasite systems including P.falcimarum infections in humans. Based on this information, it was decided that the MAP would be used as the basis of a vaccine and would be tested in humans. A pilot lot of MAP has been synthesized by a commercial laboratory capable of production under GMP and a GMP lot is being planned for formulation with alum. The MAP has been characterized by HPLC, SDS-PAGE, gel filtration, amino acid analysis, mass spectrometry, reactivity with reference monoclonal antibody, and immunogenicity and human trials are planned for the near future.