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


ABSTRACT: 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 Q? 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.

SUBMITTER: Mogus AT 

PROVIDER: S-EPMC7765226 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Mogus Alemu Tekewe AT   Liu Lihong L   Jia Manxue M   Ajayi Diane T DT   Xu Kai K   Kong Rui R   Huang Jing J   Yu Jian J   Kwong Peter D PD   Mascola John R JR   Ho David D DD   Tsuji Moriya M   Chackerian Bryce B  

Vaccines 20201215 4


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  ...[more]

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