CHO-produced RBD-Fc subunit vaccines with alternative adjuvants generate immune responses against SARS-CoV-2

PLoS One. 2023 Jul 14;18(7):e0288486. doi: 10.1371/journal.pone.0288486. eCollection 2023.

Abstract

Subunit vaccines feature critical advantages over other vaccine platforms such as stability, price, and minimal adverse effects. To maximize immunological protection of subunit vaccines, adjuvants are considered as main components that are formulated within the subunit vaccine. They can modulate adverse effects and enhance immune outcomes. However, the most suitable formulation providing the best immunological outcomes and safety are still under investigation. In this report, we combined recombinant RBD with human IgG1 Fc to create an RBD dimer. This fusion protein was expressed in CHO and formulated with alternative adjuvants with different immune activation including Montanide ISA51, Poly (I:C), and MPLA/Quil-A® as potential vaccine candidate formulations. Using the murine model, a potent induction of anti-RBD IgG antibodies in immunized mice sera were observed. IgG subclass analyses (IgG1/IgG2a) illustrated that all adjuvanted formulations could stimulate both Th1 and Th2-type immune responses in particular Poly (I:C) and MPLA/Quil-A®, eliciting greater balance. In addition, Montanide ISA51-formulated RBD-Fc vaccination provided a promising level of neutralizing antibodies against live wild-type SARS-CoV-2 in vitro followed by Poly (I:C) and MPLA/Quil-A®, respectively. Also, mice sera from adjuvanted formulations could strongly inhibit RBD:ACE2 interaction. This study offers immunogenicity profiles, forecasted safety based on Vaccine-associated enhanced disease (VAED) caused by Th1-skewed immunity, and neutralizing antibody analysis of candidates of RBD-Fc-based subunit vaccine formulations to obtain an alternative subunit vaccine formulation against SARS-CoV-2.

MeSH terms

  • Adjuvants, Immunologic
  • Adjuvants, Pharmaceutic
  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19* / prevention & control
  • Humans
  • Immunity
  • Immunoglobulin G
  • Mice
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Subunit

Substances

  • Monatide (IMS 3015)
  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Vaccines, Subunit
  • Adjuvants, Pharmaceutic
  • Immunoglobulin G
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This study received financial support from Graduate School of Chulalongkorn University in the form of a Research Assistant scholarship award (GCUGE17) received by SL. This project was also financially supported by the Government Pharmaceutical Organization (GPO) in the form of a grant (02/2564). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.