Accelerating discovery of an efficacious Plasmodium vivax multivalent multi-stage vaccine

Project Summary/Abstract
Plasmodium vivax is the second leading cause of malaria and the most prevalent cause of malaria outside of
Africa. The estimated cost of the global burden of vivax malaria is $1.4 - $4 billion per year and more people
live at risk worldwide from P. vivax than P. falciparum. It is endemic mostly in poor countries where access to
affordable health care is lacking, which leads to lost adult productivity. Relapse infections from P. vivax
poses a special challenge to malaria elimination and eradication because of its ability to repeatedly restart
blood-stage infections from hypnozoites – the dormant parasite that can persist in human livers from weeks
to years after the sporozoite infection. Exacerbating the problem, P. vivax transmission occurs prior to onset
of clinical signs and treatment options to clear relapsing parasites in the dormant liver stage are limited. The
goal of this U01 project is to accelerate vivax malaria vaccine development by validation of an optimal
combination of P. vivax target antigens in pre-erythrocytic stages. Our vaccine strategy seeks to validate
candidate antigens that together can effectively inhibit sporozoite infection and block liver stage
development, including blood stage breakthrough infection. Our strategy exploits our new in vitro functional
assay for experimental studies of liver stage development of P. vivax. We will pursue a structural vaccinology
approach, using broadly neutralizing binding inhibitory antisera and monoclonal antibodies to identify and
characterize the highest value immunogens and vaccine delivery method to design a multivalent vaccine to
prevent and eliminate vivax malaria.

Grant Number: 5U01AI155361-05
NIH Institute/Center: NIH
Principal Investigator: John Adams