Evaluation of Drug and Vaccine Candidates in the Human Malaria/Aotus Monkey Model

摘要

This report presents data: 1) On the evaluation of antimalarial drugs, and 2) plasmid DNA and recombinant protein malaria vaccines in the Aotus/ Plasmodium falciparum and vivax model. During the course of these experiments neither Aotus immunized ID with AMA-1, EBA-1 75 and MSP-1 plasmids alone or in combination with or without aGMCSF were protected against a P. falciparum FVO challenge A C2A clone P. falciparum was adapted to intact and splenectomized Aotus. Chloroquine resistance reversal was achieved in Aotus infected with the AMRU-1 strain of P. vivax by using chloroquine and prochiorperazine in combination. Oligodeoxynucleotides when given intramuscularly to Aotus improved immunogenicity of a P. falciparum PADRE 45 peptide immunogen. A significant degree cross-protector was developed in FVO immune Aotus that were challenged with an heterologous CAMP strain of P. falciparum. Immunization with a plasmid encoding region II of EBA-1 75 followed with a recombinant protein boost, partially protected Aotus monkeys against P. falciparum challenge. Both Artelinic Acid and Artesunic Acid at 8-32 mg/kg orally for five days were effective at clearing parasitemia in P. falciparum FVO inoculated Aotus. Aotus immunized with plasmids and/or recombinant MSP142 were partially protected against a P. falciparum FVO challenge.