Immunogenicity Study In Adjuvant Candidates, MDP-11 And α-Mannatide, Formulation Of Plasmodium Falciparum Vaccine M.RCAg-1

Malaria, AIDS and Tuberulosis are the three most infectious diseases in the world. Malaria remains a threat to human health. According to the report from WHO in 2014, this disease took about 528 000 lives in 2013, mostly of which are children under five years of age and pregnant women in Africa. This means 1446 young lives are lost to malaria every day. Recently, the emerging of kinds of drug-resistant parasites and insecticide-resistant female Anopheles made severse challenges for traditional prevention and treatment of malaria. Therefore, a safe,cost-efficient and economic malaria vaccine are urgent needed to reduce malaria morbidity and mortality and to control the damages brought by malaria.The immune effects were not satisfacted when Plasmodium falciparum erythrocytic stage vaccine candidates were singlely or simple combine used. Therefore constructing multi-antigens and multi-epitopes recombinant protein vaccine become one direction for blood stage malaria vaccine research. Our lab previously has constructed malaria random constructed antigen-1(M.RCAg-1) using’epitode reshuffling’ technique. As a Falciparum polyepitope artificial random recombinant protein vaccine, RCAg-1 has been proved strong immunogenicity and protective in vitro and in vivo in BALB/C mice, rabbits and NHPs models. And cooperation with the Institute of Process Engineering,the Chinese Academy of Sciences,we developed a stable purification process, established a simple and feasible stable pilot-scale preparation.On the basis of previous study, we select two highly potential clinical application adjuvants, Muramyl Dipeptide derivative and a-Mannatide, to increase the immunogenicity of vaccine M.RCAg-1. And then evaluate the immunogenicity of M.RCAg-1 in BALB/c mice to find the best adjuvant and its dose. In all, our research formed the foundation for the following clinic study of M.RCAg-1.This research mainly made the following progress:We selected the adjuvant MDP-11 and a-Mannatide which could enhance the immunogenicity of M.RCAg-1 more significantly than other formulated adjuvants with M.RCAg-1 and determined its immune dose of 100μg for mouse is appropriate.The BALB/c mice were vaccined by the recombinant protein vaccine M.RCAg-1 combined with MDP-11, α-Mannatide, MDP-11+ α-Mannatide and Freund’s adjuvant. After third immunication, serum antibody and spleen lymphocytes of the mice were analyzed. According to the results, it was preliminarily confirmed that MDP-11 is a prospective adjuvant of vaccine M.RCAg-1.