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Vaccination trials in rhesus monkeys with a minor, invariant, Plasmodium knowlesi 66 kD merozoite antigen
J A Deans1, A M Knight, W C Jean
1Department of Immunology, UMDS, Guy's Hospital Medical School, London.
Abstract:
A minor Plasmodium knowlesi 66 kD antigen, which plays an essential role in merozoite invasion, has been shown to be stable in distinct variants and strains of the parasite, and in the face of a specific immune response from the host. Parasites were unable to produce novel molecule(s) to replace it functionally, even in the presence of specific immune pressure. Rhesus monkeys immunized with the purified 66 kD antigen, with saponin as adjuvant, produced antibody which inhibited merozoite invasion of red cells in vitro. Four out of six immunized rhesus monkeys demonstrated clinically effective immunity when challenged at a time of known or presumed high inhibitory antibody titre. When immunization failed to protect, it was ascribed to insufficient levels of specific antibody attributable either to a suboptimal dose of antigen or the use of an inadequate adjuvant.
Insights
A Plasmodium knowlesi antigen essential for red blood cell invasion is stable against immune pressure. Immunization of rhesus monkeys with this antigen induced protective immunity against malaria.
Area of Science:
- Parasitology
- Immunology
- Malariology
Background:
- Plasmodium knowlesi malaria poses a significant threat.
- Merozoite invasion of red blood cells is a critical stage in the Plasmodium life cycle.
- A specific 66 kD antigen is vital for this invasion process and shows remarkable stability.
Purpose of the Study:
- To investigate the stability of the Plasmodium knowlesi 66 kD antigen under immune pressure.
- To evaluate the immunogenicity and efficacy of this antigen as a vaccine candidate in a non-human primate model.
Main Methods:
- Purified 66 kD antigen was used to immunize rhesus monkeys with saponin as an adjuvant.
- In vitro assays were performed to assess antibody-mediated inhibition of merozoite invasion.
- Monkeys were challenged with Plasmodium knowlesi to evaluate clinical immunity.
Main Results:
- The 66 kD antigen remained functionally stable despite host immune responses and parasite variations.
- Immunization elicited antibodies that inhibited merozoite invasion in vitro.
- Four out of six immunized monkeys showed effective clinical immunity upon challenge.
Conclusions:
- The Plasmodium knowlesi 66 kD antigen is a promising vaccine candidate due to its stability and ability to elicit protective immunity.
- Failure in protection was linked to insufficient antibody levels, suggesting optimization of antigen dose and adjuvant is crucial for vaccine development.