It is likely that a CTL-eliciting component will be required for an effective HIV-1 vaccine. To date, only the recombinant adenovirus-5 vaccine has been a candidate for such a component, but it faced significant issues with vector immunity and had unknown capacity to access mucosal tissues. Nanoparticles offer some advantages as vaccine vectors, but face problems with immunogenicity, carcinogenicity, and manufacturing quality. This proposal explores the use of biological nanoparticles (""""""""vaults"""""""") composed of autologous human proteins, loaded with HIV-1 sequences to serve as a vaccine. Vaults have been shown to be immunogenic for CTL responses and access the mucosal immune system. Additionally, they are composed of self-proteins that are normally found in the cytoplasm and therefore should not be immunogenic or carcinogenic, and are readily manufactured with consistent quality. The two aims will be:
Aim 1 : To create targeted vaults carrying conserved HIV-1 protein sequences;
Aim 2 : To confirm the immunogenicity of the vaults in systemic and mucosal immune compartments.
Expense, toxicity, and growing viral resistance to drug treatments for HIV-1 underscore the need for biological prevention and treatment. This project explores a potential biological strategy that could be applied to preventive or therapeutic vaccines.
|Ding, Ke; Zhang, Xing; Mrazek, Jan et al. (2018) Solution Structures of Engineered Vault Particles. Structure 26:619-626.e3|