Volume 13 Supplement 1

Challenges in malaria research: Core science and innovation

Open Access

Towards a multi-antigen multi-stage malaria vaccine

  • Adrian VS Hill1,
  • Sumi Biswas1,
  • Simon Draper1,
  • Thomas Rampling1 and
  • Arturo Reyes-Sandoval1
Malaria Journal201413(Suppl 1):O31


Published: 22 September 2014

A highly effective malaria vaccine is a major goal of global health research and will likely require a multi-stage product. Oxford researchers are developing the concept of a highly effective multi-stage P. falciparum vaccine to the point of proof-of-concept phase II testing in Europe, prior to trials in malaria-endemic areas.

Remarkable recent advances in vaccine design for all four stages of the P. falciparum parasite’s life-cycle allow testing of a multi-stage multi-component vaccine for the first time, with strong chances of success. These advances are i) the availability of a new vectored prime-boost vaccination regime based on the chimpanzee adenovirus technology that has been found to induce exceptionally potent CD8+ T cell responses and high titre antibodies against multiple malaria antigens; ii) the development of an improved virus-like particle (VLP) version of the leading partially protective RTS,S sporozoite vaccine candidate, termed R21, that lacks the excess of HBsAg in RTS,S; iii) the identification, using a vector technology screen, of the blood-stage antigen RH5 as the first antigen to induce potent strain-transcending neutralization of blood-stage parasites in in vitro growth inhibition assays; and iv) the demonstration that antibodies against a mosquito-stage antigens that induce 100% transmission blocking against field isolates of P. falciparum in Africa are inducible by a new nanoparticle vaccine candidate.

In parallel similar approaches using vectors and VLPs are underway to target the pre-erythrocytic stages of P. vivax, including the hypnozoite, and a phase I trial of the vivax blood-stage vaccine candidate, PvRII, is nearing completion.

We are aiming to undertake phase I/II clinical trials to assess the P. falciparum pre-erythrocytic, blood-stage and mosquito-stage components individually, and then together, using state-of-the art immunomonitoring, key functional assays of vaccine-induced immunogenicity, and sporozoite and blood-stage parasite challenges to measure efficacy prior to field testing. An update on this programme will be presented. A viral vectored prime-boost regime has recently shown high efficacy against malaria infection in East Africa and the first combination trial of RTS,S/AS01 with these vectors has been completed.

The prospects for achieving high efficacy with such combination approaches now appear very good.

Authors’ Affiliations

University of Oxford


© Hill et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


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