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A Glycosylated RBD Protein Induces Enhanced Neutralizing Antibodies against Omicron and Other Variants with Improved Protection against SARS-CoV-2 Infection.
Shi, Juan; Zheng, Jian; Tai, Wanbo; Verma, Abhishek K; Zhang, Xiujuan; Geng, Qibin; Wang, Gang; Guan, Xiaoqing; Malisheni, Moffat M; Odle, Abby E; Zhang, Wei; Li, Fang; Perlman, Stanley; Du, Lanying.
  • Shi J; Institute for Biomedical Sciences, Georgia State Universitygrid.256304.6, Atlanta, Georgia, USA.
  • Zheng J; Lindsley F. Kimball Research Institute, New York Blood Centergrid.250415.7, New York, New York, USA.
  • Tai W; Department of Microbiology and Immunology, and Department of Pediatrics, University of Iowagrid.214572.7, Iowa City, Iowa, USA.
  • Verma AK; Lindsley F. Kimball Research Institute, New York Blood Centergrid.250415.7, New York, New York, USA.
  • Zhang X; Department of Microbiology and Immunology, and Department of Pediatrics, University of Iowagrid.214572.7, Iowa City, Iowa, USA.
  • Geng Q; Lindsley F. Kimball Research Institute, New York Blood Centergrid.250415.7, New York, New York, USA.
  • Wang G; Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, Minnesota, USA.
  • Guan X; Institute for Biomedical Sciences, Georgia State Universitygrid.256304.6, Atlanta, Georgia, USA.
  • Malisheni MM; Institute for Biomedical Sciences, Georgia State Universitygrid.256304.6, Atlanta, Georgia, USA.
  • Odle AE; Institute for Biomedical Sciences, Georgia State Universitygrid.256304.6, Atlanta, Georgia, USA.
  • Zhang W; Department of Microbiology and Immunology, and Department of Pediatrics, University of Iowagrid.214572.7, Iowa City, Iowa, USA.
  • Li F; Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, Minnesota, USA.
  • Perlman S; Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, Minnesota, USA.
  • Du L; Center for Coronavirus Research, University of Minnesota, Saint Paul, Minnesota, USA.
J Virol ; 96(17): e0011822, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-1992935
ABSTRACT
SARS-CoV-2 has mutated frequently since its first emergence in 2019. Numerous variants, including the currently emerging Omicron variant, have demonstrated high transmissibility or increased disease severity, posing serious threats to global public health. This study describes the identification of an immunodominant non-neutralizing epitope on SARS-CoV-2 receptor-binding domain (RBD). A subunit vaccine against this mutant RBD, constructed by masking this epitope with a glycan probe, did not significantly affect RBD's receptor-binding affinity or antibody-binding affinity, or its ability to induce antibody production. However, this vaccine enhanced the neutralizing activity of this RBD and its protective efficacy in immunized mice. Specifically, this vaccine elicited significantly higher-titer neutralizing antibodies than the prototypic RBD protein against Alpha (B.1.1.7 lineage), Beta (B.1.351 lineage), Gamma (P.1 lineage), and Epsilon (B.1.427 or B.1.429 lineage) variant pseudoviruses containing single or combined mutations in the spike (S) protein, albeit the neutralizing antibody titers against some variants were slightly lower than against original SARS-CoV-2. This vaccine also significantly improved the neutralizing activity of the prototypic RBD against pseudotyped and authentic Delta (B.1.617.2 lineage) and Omicron (B.1.1.529 lineage) variants, although the neutralizing antibody titers were lower than against original SARS-CoV-2. In contrast to the prototypic RBD, the mutant RBD completely protected human ACE2 (hACE2)-transgenic mice from lethal challenge with a prototype SARS-CoV-2 strain and a Delta variant without weight loss. Overall, these findings indicate that this RBD vaccine has broad-spectrum activity against multiple SARS-CoV-2 variants, as well as the potential to be effective and have improved efficacy against Omicron and other pandemic variants. IMPORTANCE Several SARS-CoV-2 variants have shown increased transmissibility, calling for a need to develop effective vaccines with broadly neutralizing activity against multiple variants. This study identified a non-neutralizing epitope on the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, and further shielded it with a glycan probe. A subunit vaccine based on this mutant RBD significantly enhanced the ability of prototypic RBD against multiple SARS-CoV-2 variants, including the Delta and Omicron strains, although the neutralizing antibody titers against some of these variants were lower than those against original SARS-CoV-2. This mutant vaccine also enhanced the protective efficacy of the prototypic RBD vaccine against SARS-CoV-2 infection in immunized animals. In conclusion, this study identified an engineered RBD vaccine against Omicron and other SARS-CoV-2 variants that induced stronger neutralizing antibodies and protection than the original RBD vaccine. It also highlights the need to improve the effectiveness of current COVID-19 vaccines to prevent pandemic SARS-CoV-2 variants.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / COVID-19 Vaccines / COVID-19 / Antibodies, Viral Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: J Virol Year: 2022 Document Type: Article Affiliation country: Jvi.00118-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / COVID-19 Vaccines / COVID-19 / Antibodies, Viral Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: J Virol Year: 2022 Document Type: Article Affiliation country: Jvi.00118-22