Drug and Vaccine Evaluation in the Human Aotus Plasmodium Falciparum Model

摘要

The purpose of this report is to present data on the evaluation of drugs and vaccines in the human malaria/Aotus lemurinus lemurinus monkey model experimentally infected with Plasmodium falciparum or vivax. During the course of these experiments multiple drug resistance of the highly pathogenic C2A clone of P. falciparum was observed when Aotus were treated with Mefloquine (WR142490) at 40 mg/kg orally once. Quinine (WR297608) at 10 mg/kg for five days alone or once at 10 mg/kg followed by two days with PS26 (WR283178) at 10 mg/kg; and PS26 alone at 40 mg/kg for three days. The Uganda Palo Alto (UPA) strain of P. falciparum could not be adapted to Aotus. Reduction of efficacy and immunogenicity of plasmid DNA vaccines in a prime-recombinant protein boost schedule cannot be attributed to plasmid concentrations in immunized Aotus. PS26 (WR283178, BQ30798) at 2.5-20 mg/kg orally for three days cured P. falciparum Indochina I infections in Aotus monkeys. R-66-1 (WR288911, BQ34018) at 1.25-5 mg/kg orally for three days cured infections of P. falciparum Indochina I in Aotus. In contrast, GSQ7302 when given orally at 30 mg/kg twice a day for five days did not.