Glycosylated Delta-receptor-binding domain mucosal vaccine elicits broadly neutralizing antibodies with protection against SARS-CoV-2 challenge

Xiaoqing Guan; Abhishek K Verma; Gang Wang; Juan Shi; Stanley Perlman; Lanying Du

doi:10.1016/j.isci.2023.108033

Glycosylated Delta-receptor-binding domain mucosal vaccine elicits broadly neutralizing antibodies with protection against SARS-CoV-2 challenge

iScience. 2023 Sep 27;26(10):108033. doi: 10.1016/j.isci.2023.108033. eCollection 2023 Oct 20.

Authors

Xiaoqing Guan¹, Abhishek K Verma², Gang Wang¹, Juan Shi¹, Stanley Perlman^{2

3}, Lanying Du¹

Affiliations

¹ Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
² Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
³ Department of Pediatrics, University of Iowa, Iowa City, IA, USA.

Abstract

Mucosal COVID-19 vaccines are needed to block SARS-CoV-2 infection at the mucosal site. Intranasal delivery of a glycosylated Delta variant receptor-binding domain (Delta-RBD) mucosal vaccine elicited potent and balanced systemic antibody titers comparable to those induced by the intramuscular injection of the same vaccine or Omicron-S subunit vaccine, as well as high mucosal IgA antibody responses. It elicited broadly neutralizing antibodies against the original SARS-CoV-2 strain, Delta and Omicron BA1/BA2 variants, completely protecting transgenic mice from lethal challenge with a Delta variant, including complete absence of weight loss. Of note, intramuscular priming with the Omicron-S protein followed by intranasal boosting with the Delta-RBD protein improved the vaccine's ability to generate broad-spectrum neutralizing antibodies against recent BA5 and XBB Omicron variants. Overall, this vaccine has the potential to prevent the SARS-CoV-2 infection of the respiratory mucosa, while the i.m. priming and i.n. boosting vaccination strategy may offer protection against known and emerging SARS-CoV-2 variants.

Keywords: Immunology; Virology.

Abstract

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