Modelling of immune response to viral protein immunogens
Research type
Research Study
Full title
An experimental medicine study modelling the interaction between rationally-designed synthetic model viral protein immunogens and the breadth of the induced B and T cell repertoires.
IRAS ID
251930
Contact name
Katrina Pollock
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
1 years, 7 months, 23 days
Research summary
Research Summary
EVAI2020_01 is a single blinded two part experimental medicine study to determine the extent to which different prime-boost combinations of model immunogens based on HIV-1 envelope proteins (ConM and ConS), influence the breadth of viruses neutralised by induced antibodies and the associated diversity of B and T cell responses.
We will also investigate the effect of a second immunisation challenge with a combination of three model mosaic envelope proteins designed to increase the breadth of induced antibody neutralisation.
The primary outcome will be measurement of specific viral neutralisation activity of serum antibodies. Exploratory outcomes will include characterisation of blood B and T cell responses to these model immunogens.
Summary of Results
The study team would like to thank the volunteers who generously gave their time to this study. The EAV2020_01 study was sponsored by Imperial College London, and took place with funding from the European Commission in the H2020 Framework Programme (European AIDS Vaccine Initiative 2020). The study was at the NIHR Imperial Clinical Research Facility in London from March 2019 to December 2023.
Unlike some simpler viruses, it is difficult for humans to make protective antibodies against HIV. Antibodies are very important for protecting against infection. Some parts of the outer coat of HIV, which are usually hidden, may be important for making protective antibodies.
For the EAVI2020_01 study we designed some “model” proteins, based on natural proteins, to investigate how the body responds to specific protein shapes and combinations. They were given as an injection into the arm combined with other components to stimulate the immune system. They are all synthetic (manufactured in a factory) and pose no risk of infection. They are very subtle variations of naturally occurring proteins produced by viruses, in this case HIV virus.
The purpose of the study was to see if the injections would stimulate an immune response. In particular, the study tested for antibodies to HIV. As the study only used tiny proteins and no actual virus, participants were not exposed to live HIV virus by the injection. Participants were monitored for safety throughout the study by the clinical team.
117 adult volunteers who were not living with HIV participated and were assigned to one of the study groups to receive a different combination of the model proteins. Participants in Groups A to I performed very similarly in that they all produced good levels of antibodies against multiple HIV model proteins (immunogens). Groups J to L were a little different in that they only produced antibodies against the immunogen that was matched to the injection. Group M performed the best (from within groups J to M), with these participants producing antibodies against multiple HIV immunogens, mostly likely because participants in this group received the full cocktail of immunogens. Irrespective of the groups the antibodies produced were not very good at neutralising HIV and therefore would be unlikely to prevent HIV infection.
These data do show that giving this kind of injection can stimulate an immune response and this is a step in building an approach for a new vaccine against HIV.
You can learn more about this study at ClinicalTrials.gov. To find out more about research and how you can participate, contact the NIHR Imperial Clinical Research Facility by email; imperial.crf@nhs.net or phone; +44 (0)20 3313 8070.REC name
London - Fulham Research Ethics Committee
REC reference
18/LO/2196
Date of REC Opinion
14 Feb 2019
REC opinion
Further Information Favourable Opinion