SARS-CoV-2 spike protein S1 subunit induces potent neutralizing responses in mice and is effective against Delta and Omicron variants

Mamedov T., Yuksel D., Gurbuzaslan I., Gulec B., Mammadova G., Ozdarendeli A., ...More

Frontiers in Plant Science, vol.14, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 14
  • Publication Date: 2023
  • Doi Number: 10.3389/fpls.2023.1290042
  • Journal Name: Frontiers in Plant Science
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Directory of Open Access Journals
  • Keywords: delta, Omicron variants, plant transient expression system, S1 subunits of spike protein, SARS-CoV-2
  • Akdeniz University Affiliated: Yes


SARS-CoV-2, the virus responsible for the COVID-19 pandemic, belongs to the betacoronavirus genus. This virus has a high mutation rate, which rapidly evolves into new variants with different properties, such as increased transmissibility or immune evasion. Currently, the most prevalent global SARS-CoV-2 variant is Omicron, which is more transmissible than previous variants. Current available vaccines may be less effective against some currently existing SARS-CoV-2 variants, including the Omicron variant. The S1 subunit of the spike protein of SARS-CoV-2 has been a major target for COVID-19 vaccine development. It plays a crucial role in the virus’s entry into host cells and is the primary target for neutralizing antibodies. In this study, the S1 subunit of the spike protein of SARS-CoV-2 was engineered and produced at a high level in Nicotiana benthamiana plant. The expression level of the recombinant S1 protein was greater than the 0.5-g/kg fresh weight, and the purification yield was at least ~0.3 g of pure protein/kg of plant biomass, which would make a plant-produced S1 antigen an ideal vaccine candidate for commercialization. Purified, the plant-produced SARS-CoV-2 S1 protein exhibited significantly higher binding to the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2). Moreover, we also show that recombinant S1 protein/antigen-elicited antibodies can neutralize the Delta or Omicron variants. Collectively, our results demonstrate that a plant-produced S1 antigen could be a promising vaccine candidate against SARS-CoV-2 variants including Omicron.