Biomaterial Database

Virus-Like Particle Based Vaccines Elicit Neutralizing Antibodies against the HIV-1 Fusion Peptide. 2020

Alemu Tekewe Mogus, and Lihong Liu, and Manxue Jia, and Diane T Ajayi, and Kai Xu, and Rui Kong, and Jing Huang, and Jian Yu, and Peter D Kwong, and John R Mascola, and David D Ho, and Moriya Tsuji, and Bryce Chackerian

Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131, USA.

Broadly neutralizing antibodies (bnAbs) isolated from HIV-infected individuals delineate vulnerable sites on the HIV envelope glycoprotein that are potential vaccine targets. A linear epitope within the N-terminal region of the HIV-1 fusion peptide (FP8) is the primary target of VRC34.01, a bnAb that neutralizes ~50% of primary HIV isolates. FP8 has attracted attention as a potential HIV vaccine target because it is a simple linear epitope. Here, platform technologies based on RNA bacteriophage virus-like particles (VLPs) were used to develop multivalent vaccines targeting the FP8 epitope. Both recombinant MS2 VLPs displaying the FP8 peptide and Qβ VLPs displaying chemically conjugated FP8 peptide induced high titers of FP8-specific antibodies in mice. Moreover, a heterologous prime-boost-boost regimen employing the two FP8-VLP vaccines and native envelope trimer was the most effective approach for eliciting HIV-1 neutralizing antibodies. Given the potent immunogenicity of VLP-based vaccines, this vaccination strategy-inspired by bnAb-guided epitope mapping, VLP bioengineering, and prime-boost immunization approaches-may be a useful strategy for eliciting bnAb responses against HIV.