Enhancing neutralizing antibodies against receptor binding domain of SARS-CoV-2 by a safe natural adjuvant system

Virus Res. 2023 Mar;326:199047. doi: 10.1016/j.virusres.2023.199047. Epub 2023 Jan 21.


The receptor binding domain (RBD) plays a pivotal role in the viral entry as it enables the engagement of severe acute respiratory syndrome 2 (SARS-CoV-2) with the human angiotensin-converting enzyme 2 (ACE2) receptor for host cell entry. RBD is the major target for developing viral inhibitors and vaccines. Expression of recombinant RBD in E.coli is highly scalable with a low-cost procedure despite its high expression level compared to expression in mammalian and yeast cells. Using an alternative natural adjuvant system instead of alum adjuvant, increased immunogenicity of RBD antigen in serological assay including direct ELISA and surrogate Virus Neutralization Test (sVNT) was demonstrated with high levels of IgGs and neutralizing antibodies in mice sera immunized with RBD:AlSa (Alum and Sodium alginate) formulation. The sVNT is a simple and fast test that can be used instead of the conventional virus neutralization test requiring live virus and BSL3 laboratory to detect total neutralizing antibodies against RBD. Additionally, results showed a safety profile for sodium alginate which supported using it as an alternative natural adjuvant.

Keywords: Natural adjuvant; Sodium alginate; Surrogate virus neutralization test; The receptor binding domain; vaccine delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19*
  • Humans
  • Mammals
  • Mice
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus / chemistry


  • aluminum sulfate
  • Antibodies, Blocking
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2