Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains

Qiong Zhang; Shashi K Tiwari; Shaobo Wang; Lingling Wang; Wanyu Li; Lingzhi Zhang; Stephen A Rawlings; Yong Cheng; Jesse V Jokerst; Tariq M Rana

doi:10.1101/2022.04.28.489834

Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains

bioRxiv [Preprint]. 2022 Apr 28:2022.04.28.489834. doi: 10.1101/2022.04.28.489834.

Authors

Qiong Zhang^{1

2}, Shashi K Tiwari^{1

2}, Shaobo Wang¹, Lingling Wang¹, Wanyu Li¹, Lingzhi Zhang¹, Stephen A Rawlings³, Yong Cheng⁴, Jesse V Jokerst⁴, Tariq M Rana¹

Affiliations

¹ Division of Genetics, Department of Pediatrics, Program in Immunology, Institute for Genomic Medicine, UCSD Center for AIDS Research, University of California San Diego, 9500 Gilman Drive MC 0762, La Jolla, California 92093, USA.
² These authors contributed equally to this work.
³ Division of Infectious Diseases, Department of Medicine, UCSD Center for AIDS Research, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
⁴ Department of NanoEngineering, University of California San Diego 9500 Gilman Drive, La Jolla, CA 92093.

Abstract

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-viral antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

Keywords: SARS antibodies; Spike protein; mRNA vaccine; multivalent vaccine design; receptor binding domain.

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Preprint

Abstract

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