Last Updated: 27/05/2025
Coadministration of capsid modified adenovirus for malaria vaccine development
Objectives
This proposal will build on the group experience of developing chimeric recombinant proteins and recombinant adenovirus vectors to develop a coadministration vaccination regimen that combines these two vaccine platforms.
The overall goal of this research proposal is to simplify the immunization schedule by reducing the need for boosting at regular intervals. Existing adenovirus vectors will be modified to express a Plasmodium multi-stage protective antigen as a transgene by insertion of a promiscuous T cell epitope within the capsid structure.
The specific aims are to:
- Characterize and compare the effect of the insertion of T cell epitopes within the capsid on the immunogenicity of recombinant adenovirus vectors.
- Determine the immunogenicity and protective efficacy of a coadministration regimen using the P. yoelii model.
- Assess the immunogenicity of a coadministration regimen tailored for P. vivax. We will use adenovirus serotype 5 (Ad5) and the chimeric Ad5/3 vectors for capsid modification.
This studies will provide valuable data to improve the protective immune response induced by protein-based vaccines.
Plasmodium vivax is the most widely distributed human malaria parasite responsible for 80% of the clinical cases in South and Southeast Asia and 70% in the Americas. The wider geographic distribution of P. vivax in comparison to P. falciparum is explained by the unique biological features of this parasite. Although the implementation of transmission control measures has had a significant impact on morbidity and mortality, the emergence and spread of drug-resistant parasites is a growing concern. The development of novel tools to control the disease is, therefore, a global priority.
The group hypothesizes that the high copy number of T cell epitopes displayed by capsid incorporation will significantly enhance the immune responses to the chimeric transgene product. The optimized capsid modified vectors will then be used for coadministration with the multi-stage protective antigen expressed as a recombinant protein.
Viable vectors will be used for comparative experiments in mice and the successful outcome of comparative proof-of-principle experiments with the rodent malaria parasite will guide the design of a novel P. vivax vaccination regimen.
Jul 2012 — Jun 2015
$489,974
