ABSTRACT Vaccines pave the way out of the SARS-CoV-2 pandemic. Besides mRNA and adenoviral vector vaccines, effective protein-based vaccines are needed for immunization against current and emerging variants. We have developed a virus-like particle (VLP)-based vaccine using the baculovirus-insect cell expression system, a robust production platform known for its scalability, low cost, and safety. Baculoviruses were constructed encoding SARS-CoV-2 spike proteins: full-length S, stabilized secreted S, or the S1 domain. Since subunit S only partially protected mice from SARS-CoV-2 challenge, we produced S1 for conjugation to bacteriophage AP205 VLP nanoparticles using tag/catcher technology. The S1 yield in an insect-cell bioreactor was ∼11 mg/liter, and authentic protein folding, efficient glycosylation, partial trimerization, and ACE2 receptor binding was confirmed. Prime-boost immunization of mice with 0.5 μg S1-VLPs showed potent neutralizing antibody responses against Wuhan and UK/B.1.1.7 SARS-CoV-2 variants. This two-component nanoparticle vaccine can now be further developed to help alleviate the burden of COVID-19.
【저자키워드】 SARS-CoV-2, Vaccines, nanoparticle, insect cells, 【초록키워드】 COVID-19, Vaccine, pandemic, glycosylation, immunization, variants, Protein, SARS-CoV-2 variants, mice, mRNA, Wuhan, adenoviral vector, expression, platform, Neutralizing antibody response, VLP, SARS-CoV-2 spike, subunit, help, full-length S, S1 domain, effective, Cell, robust, ACE2 receptor binding, produced, alleviate, protein-based vaccine, secreted, the SARS-CoV-2, 【제목키워드】 spike, response,