Malaria Prevention by a New Technology: Vectored Delivery of Antibody Genes
Technical Report,08 Sep 2017,07 Sep 2018
John Hopkins University Baltimore United States
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Malaria has proven refractory to conventional immunization approaches. This project explores a novel route to induction of anti-malaria immunity adeno associated virus AAV vectored transfer of genes encoding known protective monoclonal antibodies MAbs to whole animals. Using a specific technology originally applied to expression of HIV antibodies, we demonstrated that mice can be protected from Plasmodium falciparum infection by antibodies against circumsporozoite protein, an antigen found on the surface of the form of the parasite injected by mosquitoes. The current project has two specific aims 1. Identification of optimal MAbs by construction of additional vectors and assessments of protective efficacy in mice, and 2. Tests of protective efficacy of these MAbs, delivered by AAV vectors, in the non-human primate NHP Aotus nancymaa challenge model of P. falciparum infection. In this period, characterization of five MAb vectors in mice has been nearly completed. NHP trials have been hampered by technical difficulties in reproducing the published challenge protocols. Extensive efforts to establish the challenge model with the published parasite strain have been repeatedly unsuccessful. An account of these efforts is included in the report text. An alternative to the published parasite strain has been obtained, and experiments to test the infectivity of sporozoites of this strain for Aotus is underway.
- Medicine and Medical Research