Project: Globally Relevant AIDS Vaccine Europe-Africa Trials Partnership

Acronym GREAT (Reference Number: SRIA2015-1066)
Duration 01/01/2017 - 31/12/2021
Project Topic An effective prophylactic HIV-1 vaccine is critical to ending the HIV-1 epidemic. The objective of this proposal is to ensure the development of a promising cross-clade preventive HIV-1 vaccine strategy, tHIVconvsX, through collaboration between institutions in Europe and Africa. This will be achieved by: (1) Building capacity for a future efficacy trial by engaging already identified populations at documented high risk for HIV-1 from diverse clades despite preventive interventions and (2) Conducting a phase 2a clinical trial to assess the safety and immunogenicity of the tHIVconsvX vaccines and demonstrate the feasibility of an efficacy trial in these at-risk populations. These aims will ensure that at the completion of this grant, we shall be prepared to launch an appropriately designed trial to prove the vaccine efficacy, should data warrant. The much improved 2nd generation conserved mosaic tHIVconsvX vaccines are superior in specificity and match of global HIV-1 variants to previous T-cell vaccines. Building on experience from several trials with the 1st generation conserved-region vaccines, the tHIVconsvX immunogens combine the use of conserved regions, bi-valent mosaic design (increasing breadth and group M HIV-1 variant match) and protective epitopes. Conserved regions are functionally/structurally constrained; therefore, they are common to HIV-1 subtypes and mutations in them reduce viral replicative fitness. Protective epitopes are associated with low virus load in large cohorts of treatment-naive patients across four continents. The tHIVconsvX immunogens are delivered by chimpanzee adenovirus prime-poxvirus MVA boost regimen; similar regimens were proven safe and highly immunogenic in European and African adults and, for vaccines against malaria, in infants. This programme will launch the first African phase 2a trial of the tHIVconsvX vaccines in Kenya, Uganda and Zambia. Vaccine-induced immune responses will be characterized by IFN-? ELISPOT, polychromatic flow cytometry and novel functional viral inhibition assays. At-risk populations to be enrolled in this phase 2a trial have already been engaged and characterized by members of this consortium, and comprise fishing communities around Lake Victoria, male and female sex workers and men-who-have-sex-with-men in Kenya, and female sex workers in Zambia, many of whom are marginalized and underserved with respect to health care and HIV-1 services. In order to ensure sustainable trial capacity is in place for ethically engaging these populations, this project will support research partners in Africa to establish appropriate community-based research structures that can support larger studies, sustained community engagement, education and provision of healthcare and HIV services. More information about the project and its progress is available on the GREAT website.
Website visit project website
Network EDCTP2
Call Research & Innovation Action: Strategic Actions supporting large scale clinical trials

Project partner

Number Name Role Country
1 The Chancellor, the Masters and the Scholars of the University of Oxford Coordinator United Kingdom
2 Medical Research Council Partner United Kingdom
3 University of Nairobi Partner Kenya
4 Zambia Emory HIV Research Project Partner Zambia
5 Stichting International AIDS Vaccine Initiative Partner Netherlands, The
6 UVRI-IAVI HIV Vaccine program Limited Partner Uganda
7 Imperial College of Science Technology and Medicine Partner United Kingdom
8 International AIDS Vaccine Initiative Inc Partner United States