Malaria Prevention by New Technology: Vectored Delivery of Antibody Genes
Abstract
Malaria has proven refractory to conventional immunization approaches. This project explores a novel route to induction of anti-malarial 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], it was 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 had 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. Aim 1 has been accomplished. Progress has been made on Aim 2 including, critically, the demonstration that vector-delivered anti-malarial mAbs are capable of preventing liver invasion by P. falciparum sporozoites, the necessary first step in malaria infection. However, difficulties with replicating published malaria challenge protocols have hampered large-scale studies in NHPs and only a single mAb has been studied in Aotus. A new approach to efficacy studies in NHPs has been developed assessment of liver burden as an indicator of infection that will permit larger studies in the future that will address the unfinished elements of Aim 2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2020
- Accession Number
- AD1133003
Entities
People
- Gary Ketner
Organizations
- Johns Hopkins University