Development of an oral liver-targeted prime-and-trap malaria vaccine

Vaccines that efficiently stop the Plasmodium sporozoite (spz) or liver stage can provide complete protection against malarial disease and will enable eradication efforts. There are currently no FDA-approved malaria vaccines for use in humans although repeated dosing with intravenously-administered attenuated spz has shown sterile protection against challenge in multiple Phase 1-2 clinical trials. Recently, CD8+ T cells that reside in the liver, namely liver resident memory T cells or TRM cells, have been identified as key cell types in protection against liver stage infection. Vaccine strategies that increase liver TRM cells and can be readily adapted to clinical use are therefore critically needed. Such vaccines could bolster CD8+ T cell immunity and may result in T cell-focused vaccines that achieve durable, high-grade protection for persons in endemic and non-endemic regions. Our laboratory has developed a two-dose vaccine that uses a DNA prime followed by an attenuated spz boost or ‘trapping dose’ that increases liver TRM cells and achieves sterile protection. 

The University of Washington will collaborate with Johns Hopkins University to develop this more easily manufactured, more easily deliverable, and less expensive vaccine. If successful, this project will deliver an optimized prime-and-oral trap vaccine rationally designed to elicit complete protection against the Plasmodium liver stage.

NIH project details

Product Development
Vaccines (Immune Correlates)

Dec 2020 — Nov 2025

$2.48M

United States