Abstract

Malaria vaccines: current situation, challenges and strategy for the future; a developer’s perspective from the PATH Malaria Vaccine Initiative

Author(s): Christian Loucq

The new paradigm of elimination and eradication and constrained economic environment – combined with a first decade of experience – have lead the PATH Malaria Vaccine Initiative (MVI) to redefine its vaccine development strategy. This strategy has two targets: the pre-erythrocytic and sexual stages of the parasite, the latter including the parasite’s evolution inside the mosquito. It encompasses four components: the selection of new antigens, identification of presenting platforms, adjuvant development and vaccine formulation and evaluation technologies. However, the development of a malaria vaccine cannot occur in isolation from other interventions; rather, it should be carried out in coordination with them. RTS,S is now in a Phase III trial, after demonstrating levels of efficacy from 30 to 50% against clinical malaria. Bringing a partially effective vaccine to licensure and use is a long and complex process that will require efficacy as well as public health impact data. Prime-boost and attenuated sporozoite approaches are, or will be, part of the portfolio required to build on these results, the former including use of adenovirusbased platforms. Current investments in blood-stage approaches are limited to attempting to resolve the challenge of AMA1 polymorphism and to an approach aimed at blocking re-entry of merozoites into red blood cells. MVI has prioritized the development of transmission-blocking vaccines and has identified some promising projects, while also researching their regulatory pathway. Two projects targeting Plasmodium vivax are supported. As part of its strategy, MVI has adopted a new classification of projects into smallscale preclinical feasibility studies, larger translational projects and, finally, vaccine candidates, the latter requiring proof-of-concept to be established in endemic countries.