Malaria Prevention by New Technology: Vectored Delivery of Antibody Genes
Technical Report,08 Sep 2016,07 Sep 2017
John Hopkins University Baltimore United States
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Malaria has proven refractory to conventional immunization approaches. We are exploring 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. This 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 a non-human primate Aotus nancymaae model of P.falciparum infection. In this period, five MAb vectors have been constructed and fully or partially characterized in mice See below. Two of these exhibit efficacy comparable to the MAb used in our original studies and are undergoing sequence optimization that is expected to enhance efficacy. NHP trials have been hampered by technical difficulties in reproducing the published challenge protocols see below, and efforts on that aim are currently directed toward validating the challenge assay.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology