期刊
VACCINES
卷 8, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/vaccines8040765
关键词
broadly neutralizing antibody; HIV-1 fusion peptide; HIV-1 DS-SOSIP trimer; prime-boost immunizations; vaccine; virus-like particles
资金
- National Institute of Health (NIH) [R01AI124378]
- Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
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 similar to 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 beta 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.
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