The work of EAVI2020 was targeted across eight interlinked objectives. The first was to design a minimum of ten new envelope-based vaccine candidates with the aim of progressing eight to manufacture and clinical testing. These have been designed and optimised at the molecular level and have been selected based on a battery of tests. Eight structurally designed vaccine candidates were selected through preclinical and biochemical/biophysical evaluation for manufacture. Two candidates were based on consensus sequences that represented the global diversity of circulating HIV strains, three additional candidates (Mosaics), generated by computer modelling, provide and alternative strategy to cover the diversity of global HIV strains. Two additional candidates were selected from envelope sequences of HIV infected individuals that naturally make protective (neutralising) antibodies early infection. All have been successfully manufactured.
In parallel, our second objective was to develop two candidate vaccines that evoke specific white blood cells (T cells) able to kill cells infected with HIV. This work was focused on two main T cell vaccine candidates: the conserved beneficial sequences (HTI vaccine); and the conserved mosaic sequences (tHIVconsvX vaccine). These were inserted into a range of vaccine platforms (DNA, RNA, MVA, ChAd & BCG). These have been assessed in comparative preclinical models and the best candidates have progressed to early clinical evaluation.
The third main objective was the production and formulation of vaccine components (adjuvants, vectors, proteins) to be advanced for human clinical trials. Eight HIV envelope-based vaccine candidates have completed GMP manufacture, together with manufacture of our selected MLPA-liposomal adjuvant. These products have completed clinical evaluation, evaluated alone and in strategic combinations and shown to be potent novel immunogens that were considered safe and well tolerated.
GMP production of MVA and ChAd constructs expressing tHIVconsvX and HTI immunogens was completed. Both vaccine candidates have completed clinical evaluation in HIV negative individuals and the HTI immunogens in HIV positive volunteers. Both vaccine candidates were shown to be safe and highly effective in elucidating potent cellular responses.
A fourth objective was the development of Advanced Animal Models to define predictive correlates of protection. Comprehensive evaluation of a range of vaccines and adjuvants in animal models has generated promising results and their predictive utility with respect to clinical results assessed.
A fifth objective was to assess a range of novel immunogens in human clinical trials to determine safety of the approach and the ability to induce protective immune responses. We have completed seven clinical trials.
A sixth objective was the development of advanced immunological analysis to facilitate prioritisation of HIV-1 vaccines and comparative analysis of human and animal responses. These assays have been applied across preclinical and clinical studies.
The seventh objective was to develop new molecular tools to study the evolution of antibody sequences and gene expression studies. A major effort was made to rapidly define the repertoire of antibody genes and humoral responses in advanced animal models and clinical studies using a novel computational approach, novel cytof-technology and monoclonal cloning technology. These investigations have provided greater depth in understanding of vaccine-elicited immune response and provide important new tools for the wider vaccine field.
Our eighth and final objective was the generation and selection of a novel and diverse portfolio of promising HIV-1 prophylactic and therapeutic vaccine candidates for further clinical development. Particular highlights are the generation of a pipeline of novel vaccine candidates that have completed clinical evaluation, these have fed into other ongoing programs and the candidates themselves provide an important legacy of the EAVI project to be used in ongoing and future studies.
The EAVI2020 consortium raised the profile of EAVI2020 HIV vaccine research to the scientific community, stakeholders in the HIV field, policy makers, and also the wider public over the course of the project. Project data was disseminated through EAVI2020 consortium members participating in over 250 conferences, workshops, and events, as well as through the EAVI2020 website and social media accounts. We also surpassed our target of 100 scientific publications, with the total number reported as part of the project reaching 120.
