Immune responses to experimental plasmodium knowlesi H strain infection in Olive baboons (papio anubis)

Abstract

Malaria is a major and growing threat to economic development and public health and causes about 2.7 million deaths annually. Plasmodium knowlesi is an attractive experimental system for malaria research as it is phylogenetically close to P. vivax and shares many of vaccine candidate molecules. This study was carried out to determine host immunological profiles mounted by Olive baboons during the course of an infection with Plasmodium knowlesi. Immunological parameters were monitored in six adult olive baboons (Papio anubis) experimentally infected with Plasmodium knowlesi blood stage parasites. The pre-infection values served as controls against post infection values. Following primary infection these baboons developed severe (acute) or mild (chronic ) disease. The chronically infected animals were able to control parasitaemia to below 2% but parasitaemia rose steadily in acutely infected animals to above 6% before being treated. Only chronically infected animals were re-infected and were able to control the infection in peripheral circulation to sub patent levels by day 14 post re-infection. All baboons produced anti P. knowlesi IgM and 1 gG antibodies upon infection. Circulating IFNY from serum rose to an average OD of 0.217 _+ 0.015 by day 14 in acutely infected animals as compared to an OD of 0.063 _+ 0.022 in chronic animals. Recall proliferation was positive, with the highest stimulation index (SI) observed in PBMC from chronic animals at day 42 post infection (SI=10.06 _+ 2.74). In general, the SI values were higher in chronic animals than in acute animals. This was also the case with CD4 + T cell counts, where chronic animals had an average 64% increase while acute animals had 47% increase by day 14 post infection. When compared with pre-infection values, the variations in CD8 + T cell numbers in both acute and chronic animals were minimal. These studies show that P. knowlesi infected baboons mount an immune response that is characterized by an increase in IgM, IgG, and IFNy. In addition, these studies are important in validation of the P. knowlesi- baboon model for malaria drug and vaccine research