Project: Globally Relevant AIDS Vaccine Europe-Africa Trials Partnership

Acronym	GREAT (Reference Number: SRIA2015-1066)
Duration	01/01/2017 - 31/12/2021
Project Topic	The aim of this work is to advance the development of a promising global preventive HIV-1 vaccine strategy through collaboration between institutions in Europe and Africa. The working hypothesis is that focusing HIV-specific killer T cells on the most conserved regions of the HIV proteome will lead to control of HIV replication. This will be achieved by two main aims: Aim 1. Building capacity for a future efficacy trial by engaging already identified populations with documented high-risk to circulating HIV-1 from diverse clades despite preventive interventions and Aim 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 two aims will ensure that at the close of this grant, the collaborators will be prepared to launch an appropriately designed trial to test the vaccine efficacy, should data warrant. The much improved 2nd generation conserved mosaic tHIVconsvX vaccines are superior in specificity and match to global HIV-1 variants to the 1st generation of conserved-region vaccines and other previously tested T-cell vaccines. Building on experience from 8 trials with the 1st generation vaccines, the tHIVconsvX immunogens combine the use of conserved regions, bi-valent mosaic design (increasing breadth and group M HIV-1 variant match) and known protective epitopes. Conserved regions are functionally/structurally constrained; therefore, they are common to HIV-1 subtypes and mutations in them typically reduce viral replicative fitness. Protective epitopes are associated with low virus load and high CD4 counts in large cohorts of treatment-naive patients across four continents. The tHIVconsvX immunogens are delivered by non-replicating simian (chimpanzee) adenovirus prime-non-replicating 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 program will launch the first African phase 2a trial of the tHIVconsvX vaccines in Africa. Vaccine-induced immune responses will be characterized by IFN-γ 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. They 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 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. The GREAT program encompasses eight organisations with extensive research and product development expertise, Africa-based research infrastructure and community engagement and enrolling individuals at high risk of infection across Africa. Research institutes in Kenya, Uganda and Zambia and the International AIDS Vaccine Initiative (IAVI) are working with research teams from Oxford University and Imperial College London to advance the tHIVconsvX vaccine, a candidate preventative strategy designed to provide protective immunity against the various HIV strains present throughout the world. During Year 2 of this program, the main activities were Upgrade of facilities at the participating clinics and laboratories Community outreach activities and stakeholder meetings to ethically engage potential participants with the future trial Development of the Clinical Trial Protocol and supporting trial activities Development of adenoviral vectored vaccine (C1) in preparation for manufacture Updating of the project website. The address is www.great-partnership.eu/
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	Imperial College of Science Technology and Medicine	Partner	United Kingdom
3	International AIDS Vaccine Initiative Inc	Partner	United States
4	Medical Research Council	Partner	United Kingdom
5	Stichting International AIDS Vaccine Initiative	Partner	Netherlands
6	University of Nairobi	Partner	Kenya
7	UVRI-IAVI HIV Vaccine program Limited	Partner	Uganda
8	Zambia Emory HIV Research Project	Partner	Zambia