PrEPVacc is a combination HIV vaccine + pre-exposure prophylaxis (PrEP) phase IIb study using an innovative adaptive trial design. PrEPVacc is exploiting >20 years of European HIV research to demonstrate the efficacy of two regimens of experimental DNA, MVA and Env protein/adjuvant vaccines. All these PrEPVacc GMP vaccine products have already been studied in Europe and Africa in >600 volunteers, and are safe and immunogenic.

This proposal is based on prior FP5, FP7, H2020 and EDCTP-1 programmes and will leverage substantial co-funding support from IAVI, CAVD, UK MRC, Wellcome Trust and Gilead. PrEPVacc represents a consortium of highly experienced African investigators, with access to high-risk populations and accredited laboratories in Uganda, Tanzania, Mozambique and South Africa, together with broad research capacity building. PrEPVacc is an African study; the trial database, trial management, all primary laboratory assays and data analyses will be undertaken by the PIs, coordinated through MRC/UVRI, Entebbe, with technical support and capacity building from IAVI, CHUV, Imperial, LMU, KI and MRC/CTU.

The adaptive trial design is novel in the HIV vaccine field; we shall generate data on HIV vaccine efficacy and investigate correlates of protection, address adherence and attitudes to PrEP and its impact on HIV vaccine trials. The results of PrEPVacc will potentially have great impact: by testing a DNA-MVA immunisation regime with more potent T-cell and similar B-cell immunogenicity compared to the RV144 trial, the only HIV vaccine trial to have shown protective efficacy; by comparing DNA-MVA-protein with DNA-protein immunisation; by exploring universal PrEP in an HIV vaccine study population for the first time. If PrEPVacc is successful, we will have delivered a biomedical intervention to reduce HIV incidence which could be generalised and commercialised; if these vaccines fail, a new generation of candidates may be required.

The proposal is highly efficient; a novel design will allow early cessation of futile arms. The proposal is timely: phase 1&2 trials of these products have recently demonstrated safety and immunogenicity in Europe and Africa. PrEPVacc is complementary and scientifically additive to the HVTN 702 pox/protein phase 3 trial, with added potential for generating new data on B- and T-cell immunogenicity after different DNA priming strategies and the impact of PrEP on vaccine trials. PrEPVacc will strengthen South-South and South-North collaboration and promote African self-sufficiency for future trials.

Hypothesis:

1. DNA-MVA-rgp140/MPLA will induce broader and more durable immune responses and hence enhanced protection compared to RV144
2. DNA-rgp120/alum will rapidly induce high titre functional antibodies and hence enhanced protection, compared to RV144.
3. PrEP with daily or intermittent Truvada (tenofovir/emtricitabine) is protective, with up to 86% demonstrated in MSM populations