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

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

Posted 25 Sep 2020
bioRxiv DOI: 10.1101/2020.09.25.308957

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 at 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, we used platform technologies based on RNA bacteriophage virus-like particles (VLPs) to develop multivalent vaccines targeting the FP8 epitope. We produced recombinant MS2 VLPs displaying the FP8 peptide and we chemically conjugated synthetic FP8 peptides to Qβ VLPs. Both recombinant and conjugated FP8-VLPs induced high titers of FP8-specific antibodies in mice. 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 optimal prime-boost immunization strategies – may be an effective strategy for eliciting bnAb responses against HIV. ### Competing Interest Statement B.C. has equity stakes in Agilvax, Inc. and FL72, companies that do not have financial interest in HIV vaccines. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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