Next generation HIV-1 immunogens inducing broadly reactive neutralising antibodies

General

We start from the hypothesis that in HIV-1 infected individuals with HIV-1 specific broadly neutralising activity in serum, virus variants with specific envelope characteristics are present that have elicited these responses and that could elicit these responses again as a vaccine immunogen. Our goal is to gather the skills and efforts of several active research groups in trying to achieve new HIV-1 immunogens, ranging from clinical samples to small animal models.

Specific

Cloning and sequencing HIV-Env genes, and development of a genetic and functional (sensitive to antibodies) env database.High-throughput cloning, expression and purification of HIV env genes that in potential may elicit broadly Nabs and the creation of Env protein arrays.Antigen optimisation and identification of novel neutralisation-sensitive epitopes as HIV-1 vaccine candidates.Rational mutagenesis of env aimed at de-protecting highly conserved neutralisation epitopes that are kept in a cryptic conformation or at stabilising env in a conformation that optimally presents the CD4-binding site.Novel strategies for inducing inter-clade and intra-clade cross-reactive responses.Optimisation of antigen targeting to the correct cells of the immune system.Novel adjuvants for Th2 response and delivery strategies for mucosal routes.Optimisation of immunisation routes and prime-boost schedules.Exploitation of the knowledge on the mechanisms of HIV mucosal infection and mucosal immunity for the development of safe and effective vaccines capable of preventing HIV-1 infection.Development of an immunological platform with standardised procedures.