Periodic Reporting for period 6 - EAVI2020 (European AIDS Vaccine Initiative 2020)
Okres sprawozdawczy: 2021-05-01 do 2022-04-30
In parallel, our second objective have been to develop two candidate vaccines that evoke specific white blood cells (T cells) able to kill cells infected with HIV. This work has focused on two main T cell vaccine candidates: the conserved beneficial sequences (HTI vaccine); and the conserved mosaic sequences (tHIVconsvX vaccine). These have been inserted into a range of vaccine platforms (DNA, RNA, MVA, ChAd & BCG) and are being assessed in comparative preclinical models and will enter clinical evaluation in 2021.
The third main objective has been 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 entered clinical evaluation with the trials finishing in this year (2022).
GMP production of MVA and ChAd constructs expressing tHIVconsvX and HTI immunogens has been completed. Both vaccine candidates have entered clinical evaluation in HIV negative individuals and HIV positive volunteers.
A fourth objective has been the development of Advanced Animal Models to define predictive correlates of protection. Ongoing evaluation of a range of vaccines and adjuvants in animal models has been generating promising results. The predictive utility of these different models will be assessed by comparison with result derived from clinical evaluation of the same vaccine candidates.
A fifth objective is 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. Currently we have seven clinical trials underway that will be completed in 2022. Immune analysis is ongoing and will be completed in this year when the trial is completed.
A sixth objective has been the development of advanced immunological analysis to facilitate prioritisation of HIV-1 vaccines and comparative analysis of human and animal responses. A major objective of work has been the characterisation of Mosaic and acute envelope immunogens selected for the second and third wave of clinical studies. Additional work has been focussed on immunogens based of gp41 and a highly novel peptide immunogen: W614A-3S-CRM. Ongoing work is optimising advanced antibody functional assays for use in human and animal models.
The seventh objective is to develop new molecular tools to study the evolution of antibody sequences and gene expression studies. A major effort has been made to rapidly define the repertoire of antibody genes in advanced animal models using a novel computational approach, IgDiscover. We have also been developing blood cell analysis using novel cytof-technology to provide greater depth in understanding of vaccine-elicited immune response.
Our eighth and final objective is 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 have been the generation of a pipeline of novel vaccine candidates that are under evaluation in preclinical models and progressing towards early clinical testing.
The EAVI2020 consortium continue to raise the profile of EAVI2020 HIV vaccine research to the scientific community, stakeholders in the HIV field, policy makers, and also to the wider public. Project data was disseminated through EAVI2020 consortium members participating in 19 conferences, workshops, and events. We have also now surpassed our target of 100 scientific publications, with the publications submitted over this reporting period bringing the total number of scientific publications from the project to 112.
The conduct of seven clinical trials is unprecedented for a project of this size and a significant feat given the COVID-19 pandemic. The IgDiscover platform is a key new tool for international scientists to better interpret the evolution of antibody responses in animal models. The development and refinement of the Viral Inhibition Assay is allowing scientists for the first time to determine the functional activity of vaccine induced T cells to kill cells infected with HIV. In year five of the project a number of publications have been generated (35). Our innovative training program for PhD students and postgraduates is proving integral to the training of a new generation of HIV researchers.