SARS‑CoV-2 RBD219-N1C1: A yeast-expressed SARS-CoV-2 recombinant receptor-binding domain candidate vaccine stimulates virus neutralizing antibodies and T-cell immunity in mice. Issue 8 (3rd August 2021)

• Record Type: Journal Article
• Authors: Pollet, Jeroen; Chen, Wen-Hsiang; Versteeg, Leroy; Keegan, Brian; Zhan, Bin; Wei, Junfei; Liu, Zhuyun; Lee, Jungsoon; Kundu, Rahki; Adhikari, Rakesh; Poveda, Cristina; Villar, Maria Jose; de Araujo Leao, Ana Carolina; Altieri Rivera, Joanne; Momin, Zoha; Gillespie, Portia M.; Kimata, Jason T.; Strych, Ulrich; Hotez, Peter J.; Bottazzi, Maria Elena
• Is Part Of: Human vaccines & immunotherapeutics. Volume 17:Issue 8(2021)
• Page Start: 2356
• Page End: 2366
• Publication Date: 2021-08-03
• Subjects: COVID-19 -- RBD -- alum -- pseudovirus -- coronavirus -- ACE-2; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2021.1901545
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: There is an urgent need for an accessible and low-cost COVID-19 vaccine suitable for low- and middle-income countries. Here, we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast ( Pichia pastoris ), as a suitable vaccine candidate against COVID-19. After introducing two modifications into the wild-type RBD gene to reduce yeast-derived hyperglycosylation and improve stability during protein expression, we show that the recombinant protein, RBD219-N1C1, is equivalent to the wild-type RBD recombinant protein (RBD219-WT) in an in vitro ACE-2 binding assay. Immunogenicity studies of RBD219-N1C1 and RBD219-WT proteins formulated with Alhydrogel® were conducted in mice, and, after two doses, both the RBD219-WT and RBD219-N1C1 vaccines induced high levels of binding IgG antibodies. Using a SARS-CoV-2 pseudovirus, we further showed that sera obtained after a two-dose immunization schedule of the vaccines were sufficient to elicit strong neutralizing antibody titers in the 1:1, 000 to 1:10, 000 range, for both antigens tested. The vaccines induced IFN-γ IL-6, and IL-10 secretion, among other cytokines. Overall, these data suggest that the RBD219-N1C1 recombinant protein, produced in yeast, is suitable for further evaluation as a human COVID-19 vaccine, in particular, in an Alhydrogel® containing formulation and possibly in combination with other immunostimulants.