Malaria Prevention by a New Technology: Vectored Delivery of Antibody Genes
Abstract
Malaria has proven refractory to conventional immunization approaches. We are exploring a novel route to induction of antimalaria immunity: adeno associated virus (AAV) vectored introduction of genes encoding known protective monoclonal antibodies (MAbs) into whole animals. Using a technology originally applied to expression of HIV antibodies [1], we demonstrated that mice can be protected from Plasmodium infection by vector-driven expression of a monoclonal antibody (2A10) against circumsporozoite protein, an antigen found on the surface of the form of the parasite injected by mosquitoes[2]. Building on that observation, this project has two overall specific aims: 1. identification and evaluation of additional, potentially more effective, MAbs in the murine system, and 2. tests of protective efficacy of MAbs delivered by AAV vectors in a non-human primate (NHP; Aotus nancymaae ) model of P. falciparum infection. Efforts in this period have been directed primarily at Aim 2, assessing protection against malaria sporozoite infection conferred by MAb expression in NHPs. As noted in earlier Quarterly reports and in detail below, published procedures for challenging Aotus in order to determine protection, which rely upon development of parasitemia post-challenge, are not reproducible in our hands. Therefore, we have explored an alternative method of determining efficacy based on measurement of liver parasite load. Assessment of protection using the new protocol is underway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1086306
Entities
People
- Gary Ketner
Organizations
- Johns Hopkins University