Sendai virus particles carrying target virus glycoproteins for antibody induction

• Published in: Vaccine Vol. 40; no. 16; pp. 2420 - 2431
• Main Authors: Ishii, Hiroshi, Nakamura-Hoshi, Midori, Shu, Tsugumine, Matano, Tetsuro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 06.04.2022; Elsevier Limited
• Subjects: Acquired immune deficiency syndrome; AIDS; Allergy and Immunology; Animals; Antibodies; Antibodies, Neutralizing; Antibody; Antigens; antiretroviral agents; Antiviral agents; env Gene Products, Human Immunodeficiency Virus; Epitopes; Experiments; Glycoprotein; Glycoproteins; HIV; HIV Antibodies; HIV Infections; HIV-1; HTLV; Human immunodeficiency virus; Immunization; Immunogenicity; Infections; Infectious diseases; Mice; Monoclonal antibodies; Murine respirovirus; Plasmids; Proteins; Sendai virus; Sendai virus - genetics; Trimers; Vaccine; Vaccines; Vectors (Biology); Viral infections; Virion; Virions; Virus-like particles; Viruses; Vaccine; HIV; Antibody; Sendai virus; Glycoprotein; HTLV
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2022.03.008

Induction of antibodies targeting viral glycoproteins is a key for the development of a vaccine against enveloped virus infection. Glycoproteins on the virion exhibiting native multimer structure may be a good immunogen to present antibody epitopes, but it is often difficult to prepare immunogenic inactivated virions. Preparation of soluble glycoprotein multimers has been attempted, while virus-like particles carrying target glycoproteins can be a more immunogenic antigen. In the present study, a target glycoprotein-embedded Sendai virus (SeV) particle was developed for induction of anti-virus antibodies. We constructed a chimeric antigen, HIV-1 EnvF, consisting of HIV-1 Env ectodomain and SeV F transmembrane-cytoplasmic domain, which was shown to be efficiently incorporated into the SeV virion. EnvF was recognized by anti-HIV-1 broadly-neutralizing monoclonal antibodies (bnAbs) including 35O22 that targets an Env trimer-dependent epitope. Analysis revealed that HIV-1AD8 EnvF can mediate viral entry into the cells, which is inhibited by anti-HIV-1 bnAbs and HIV-1 entry inhibitors, suggesting that the EnvF exhibits an HIV-1 Env native-like functional structure to present bnAb epitopes. Immunization of mice with replication-defective SeVs expressing HIV EnvF and non-infectious SeV particles (NVP) carrying HIV EnvF efficiently induced anti-HIV Env antibodies. HTLV-1 EnvF also showed the potential to efficiently induce anti-HTLV-1 Env antibodies. These results indicate that SeV particles carrying EnvF can be a promising vaccine platform for induction of antibodies targeting enveloped virus glycoproteins.