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Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface

Hongguan Xing1,2, Liyan Zhu3,4, Pingping Wang2

  • 1Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Frontiers in Immunology
|August 29, 2022
PubMed

Insights

This study developed a novel yeast-based vaccine candidate displaying SARS-CoV-2 receptor-binding domains. This method offers a rapid, cost-effective approach for producing effective COVID-19 vaccines against emerging variants.

Area of Science:

  • Biotechnology
  • Immunology
  • Virology

Background:

  • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19, a major global health concern.
  • Vaccination is crucial for pandemic control, necessitating rapid development of effective vaccine candidates.
  • Existing vaccine production methods can be costly and time-consuming.

Purpose of the Study:

  • To develop a cost-effective and rapidly producible vaccine candidate against SARS-CoV-2 and its variants.
  • To utilize yeast surface display technology for displaying receptor-binding domains (RBDs) of SARS-CoV-2.
  • To evaluate the immunogenicity and efficacy of the developed vaccine candidate in a mouse model.

Main Methods:

  • Engineered *Saccharomyces cerevisiae* to display SARS-CoV-2 RBDs from initial strain and variants (B.1.1.7, B.1.351, B.1.617.1).
  • Utilized a *gal80* knockout strain to enable rapid protein expression without galactose induction, shortening culture time from 72h to 24h.
  • Assessed immune responses in mice vaccinated with the B.1.617.1 variant vaccine candidate, including humoral and cellular immunity.
  • Investigated the effect of double deglycosylation (N331Q and N343Q) on RBD binding affinity to ACE2 and antibody neutralization.

Main Results:

  • Successful display of SARS-CoV-2 and variant RBDs on yeast surface.
  • Demonstrated robust humoral and cellular immune responses in mice vaccinated with the B.1.617.1 vaccine candidate.
  • Antiserum from vaccinated mice showed neutralizing activity against wild-type RBD and cross-reactivity against B.1.351 and B.1.1.7 RBDs.
  • Deglycosylation significantly reduced RBD binding to ACE2 and antibody neutralization escape.

Conclusions:

  • Yeast surface display is a viable alternative for rapid, large-scale production of SARS-CoV-2 vaccine candidates.
  • The developed vaccine candidate elicits protective immune responses against SARS-CoV-2 and its variants.
  • Targeting RBDs and understanding glycosylation patterns are critical for developing broadly protective coronavirus vaccines.
Keywords:
B.1.671.1SARS-CoV-2receptor-binding domainvaccineyeast surface display

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