- The biggest challenges for vaccine development are HIV-1 diversity and escape. To tackle these, we have developed T-cell immunogen HIVconsv, which directs vaccine-induced responses to the most functionally conserved regions of the HIV-1 proteome and thus targets both diverse clades circulating in the population and escape mutants generated in infected individuals. Because these regions are functionally conserved, HIV-1 cannot easily change and escape them without a significant cost to its replicative fitness. The HIVconsv vaccines have entered 8 clinical trials and showed high immunogenicity in HIV-negative adults in Oxford and Kenya as well as in HIV-infected patients on antiretroviral treatment.
- A second generation conserved mosaic vaccines called tHIVconsvX has been developed with significantly improved coverage of global HIV-1 variants and delivery. These are being characterised in pre-clinical models and are in the pipeline for clinical trials. The tHIVconsvX-induced T-cells will complement Ab vaccines while the induction of broadly neutralising antibodies remains suboptimal and will likely be key for HIV cure.
- In collaborations, we are assessing the importance of vector priming on induction of broadly neutralizing antibodies against HIV-1. Co-delivery of antibody and T-cell vaccines will optimised.
- The laboratory aims to stay one step ahead of the clinical testing, developing improved next generation immunogens, vectors and regimens.