Adrian V. S. Hill – Director, The Jenner Institute, University of Oxford, UK
Preventing Malaria Mortality : a vaccine solution
Malaria vaccine development has reached a remarkable turning point. One candidate vaccine has completed a 16,000 subject phase III trial with mixed results but is aiming for licensure, another whole parasite approach has shown high level efficacy in the US but much less efficacy in Africa, and the first four-stage malaria vaccine is approaching African trials.
Since 1984 the circumsporozoite protein has been a leading target for vaccine developers: GSK’s RTS,S in the adjuvant AS01 induces remarkably potent antibodies to the conserved central repeat of this P. falciparum coat protein, with >50% efficacy in US controlled human malaria infection trials, but much lower efficacy in African infants. This reduced efficacy correlates with malaria-induced immunosuppression and waning of vaccine-induced antibodies with evidence of a rebound in susceptibility. A new better designed “R21” virus-like particle from Oxford in early stage trials shows higher efficacy with lower doses and a less complex adjuvant suggesting improved utility.
Liver-stage vaccines based on viral vectors and, more recently, whole sporozoites have reached African trials. Intravenously delivered irradiated sporozoites dissected from mosquitoes provide high level efficacy in US CHMI trials, but disappointingly low immunogenicity and efficacy in initial African field trials. In East African adults viral vectors have shown higher efficacy against infection. A new vectored “prime-target” immunisation strategy, based on targeting resident memory T cells to the liver, shows exceptional efficacy pre-clinically and in now in clinical trials.
A new multi-stage programme, combining R21, viral vectors and also new subunit vaccines against the blood-stage and sexual stage of the life cycle, is in clinical trials. The blood-stage vaccine, comprising the unusually conserved PfRH5 protein, induces cross-strain functional antibodies in phase I trials and is now in a phase IIa CHMI trial. Finally, a range of Pfs25-based candidate vaccines are in phase I testing, aiming to prevent transmission to mosquitoes.
This remarkable progress leverages a diverse range of leading vaccine technologies and the capacity to measure efficacy in small numbers of volunteers, and promises a high efficacy deployable vaccine to prevent disease and death caused by P. falciparum in the coming years.
Contact : Rogerio Amino (email@example.com – Poste : 82 73)