Evaluation of Drug and Vaccine Candidates in the Human Malaria/Aotus Monkey Model
Abstract
The Plasmodium falciparum 1088 strain did not adapt in Aotus Iemurinus Iemurinus when inoculated intraperitoneally. A Salvador I strain of Plasmodium vivax was adapted to splenectomized and intact Aotus after serial passage. Artelinic acid WR255663AK (JN8331) when given to Aotus by the oral route at 20 mg/kg b.i.d. for three days, appeared to be safe, and cleared a P. falciparum FVO infection. Re-treatment at 40 mg/kg cured a recrudecence that occurred 31 days PI. In vaccine studies, neither, Aotus immunized intradermally (ID) with AMA-1, EBA-175 and MSP-1 plasmid DNA vaccines alone or in combination, nor, Aotus immunized ID with AMA-1, EBA-175 and MSP-1 plasmid DNA vaccines as a combination with or without aGM-CSF, were protected against a challenge with an FVO strain of P. falciparum. However, when AMA-1, EBA-175 and MSP-1 plasmid DNA vaccines were given ID as a combination to P. falciparum FVO cured Aotus, 416 (67%) animals were protected against an homologous infection. Total absence of antibody responses were observed in Aotus after three ID immunizations with P. vivax DNA vaccines based on PvCSP, PvSSP2, PvMSP-1 p42, PvAMA1, and PvDBP(regions II-IV) alone or in combination. Homologous re-challenge with Vietnam-Oak Knoll parasites resulted in thirteen Aotus with sterile immunity after 4-6 inoculations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1998
- Accession Number
- ADA353428
Entities
People
- Nicanor Obaldia Iii.