期刊
HUMAN VACCINES & IMMUNOTHERAPEUTICS
卷 17, 期 8, 页码 2356-2366出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21645515.2021.1901545
关键词
COVID-19; RBD; alum; pseudovirus; coronavirus; ACE-2
资金
- Robert J. Kleberg Jr. and Helen C. Kleberg Foundation
- NIH [CA125123, RR024574, AI14087201]
- Baylor College of Medicine
- Texas Children's Hospital
- Cytometry and Cell Sorting Core at Baylor College of Medicine
- CPRIT Core Facility Support Award [CPRIT-RP180672]
The article discusses the development of a SARS-CoV-2 receptor-binding domain (RBD) protein expressed in yeast as a possible candidate for a low-cost COVID-19 vaccine for low- and middle-income countries. The modified recombinant protein showed promising results in in vitro and in vivo studies, inducing high levels of binding IgG antibodies and strong neutralizing antibody titers against SARS-CoV-2 pseudovirus in mice. These findings support further evaluation of the yeast-produced RBD219-N1C1 recombinant protein as a potential COVID-19 vaccine candidate, particularly when formulated with Alhydrogel and possibly combined with other immunostimulants.
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 (R) 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-gamma 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 (R) containing formulation and possibly in combination with other immunostimulants.
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