Chimeric hybrid transmission blocking vaccine for malaria
The overall goal of this NIH Exploratory/Developmental Research Grant Award (R21) is to develop and evaluate the potential of a novel chimeric construct based on Ookinete surface protein (Pvs25) as an effective Plasmodium vivax transmission-blocking vaccine (TBV). Given the emergence and spread of drug-resistant parasites, and the global malaria eradication agenda, the development of novel tools to control malaria transmission is an essential priority.
The studies proposed aim to (1) test in comparative experiments in mice the effect of a T helper module (HM) on Pvs25 immunogenicity and (2) assess the safety and immunogenicity of the novel chimeric construct in rhesus macaques. Transmission blocking immunity will be tested in vivo using a P. berghei transgenic parasite expressing Pvs25 and in vitro using standard membrane-feeding assays. These studies have the general goal of showing that a HM can be used as a carrier platform for poorly immunogenic malaria antigens.
Plasmodium vivax is the most prevalent of the human malaria parasites outside Africa with an estimated 80% of the cases in South and Southeast Asia and 70% in the Americas. Although Pvs25 vaccine constructs have reached a phase of clinical development, a main concern in the field is its poor immunogenicity. Strategies used to date to enhance the immunogenicity include changes in the delivery system and formulation. However, a clinical trial using a water-in-oil emulsion was halted due to severe systemic adverse events. New methodologies to improve safety and immunogenicity of Pvs25 are required.
Given the dramatic impact of malaria with increasing attention on the widespread and severe nature of P. vivax, and the urgent need for novel control measures to reduce transmission, our proposal has the potential to serve as the framework for future development of effective multi-stage vaccines.