HIVacToGC
HIV Vaccine Targeting via DNA Origami Nanoparticles to lymph nodes to promote Germinal Center formation
The HIVacToGC Project
HIV has so far defied all attempts to develop an effective vaccine against it. Nine efficacy trials testing several vaccine candidates have been conducted in the last 25 years, with only one of them resulting in very modest, insufficient protection. One trial, PrEPVacc is still ongoing.
Yet, in the 40 years since HIV’s disovery, a lot has been learned about the virus and the reaction of the human immune system, as well as the means how HIV escapes the immune response.
In the HIVacToGC project we aim to facilitate elicitation of the proper immune response by (1) presenting the HIV envelope protein in the form of engineered, state-of-the-art antigens on particulate carries made of DNA origami, to resemble a virus-like shape (DNA-origami nanoparticles = DONPs), (2) that additionally are formulated to undergo release over time, and (3) are designed to get targeted to germinal centers of lymph nodes, which are the anatomical sites where high-quality antibody responses are developed.
Our primary goal
Our primary goal is to provide a pre-clinically validated pharmaceutical vaccine formulation and targeting strategy (technology readiness level 5 [TRL-5]), with the potential to protect from infection (prophylactic setting) and/or control virus replication when used as cART adjunct.
Germinal Center Targeting
Reasons for the failure of Env immunogen formulations used so far to induce neutralization breadth are manifold, and include inefficient targeting of Env-immunogens to lymph nodes (LNs) and lack of engagement of germline B cell receptors (gl-BCRs) lateron giving rise to broadly neutralizing antibodies (bnAbs) after antibody affinity maturation. Those gl-BCRs are expressed on naïve B cells located in the B cell areas of lymph nodes. Thus, a key requirement toward a proper bnAb-response is efficient delivery and targeting of high-quality Env immunogens into LNs to initiate germinal center reactions and drive B cell maturation.
The Partners
An overview of the participating academic groups and industrial partners
UREG
With two working groups (UR-MV and UR-PT) the UREG team will manage the project and develop, select, produce and conjugate the cargo to the DONPs.
TUM-BN
Within the HIVacToGC project, the TUM-BN team will contribute state-of-the-art expertise in programmable self-assembling DONPs.
iTERM
Helmholtz-Institut München will provide their image and data analysis technologies to track DONP-conjugates in vivo.
tilibit nanosystems GmbH
Within the HIVacToGC project, tilibit GmbH will develop methods and SOP's for the scale-up of the production of the DNA-Nanoparticles.
2bind GmbH
Within the HIVacToGC project 2bind will work on formulation of DNA origami Nanoparticles to identify conditions to preserve Env's protein structure.