Abstract

The structures of immunogens that elicit the most potent neutralization antibodies to prevent COVID-19 infection are still under investigation. In this study, we tested the efficacy of a recombinant trimeric Spike protein containing polyI:C (PIKA) adjuvant in mice immunized by a 0–7–14 day schedule. The results showed that a Spike protein-specific antibody was induced at Day 21 with titer of above 50,000 on average, as measured by direct binding. The neutralizing titer was above 1000 on average, as determined by a pseudo-virus using monoclonal antibodies (40592-MM57 and 40591-MM43) with IC50 at 1 μg/mL as standards. The protein/peptide array-identified receptor-binding domain (RBD) was considered as immunodominant. No linear epitopes were found in the RBD, although several linear epitopes were found in the C-terminal domain right after the RBD and heptad repeat regions. Our study supports the efficacy of a recombinant trimeric Spike protein vaccine candidate for COVID-19 that is safe and ready for storage and distribution in developing countries.

Highlights

  • It is generally accepted that effective COVID-19 vaccines are the only approach to end the global pandemic

  • Inactivated virus [1], adenoviral vector-based vaccines [2,3,4], and mRNA vaccines [5,6] encoding Spike proteins have been approved for urgent use in China, the US, and other countries

  • These vaccines do not meet the need for vaccination in all countries

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Summary

Introduction

It is generally accepted that effective COVID-19 vaccines are the only approach to end the global pandemic. Inactivated virus [1], adenoviral vector-based vaccines [2,3,4], and mRNA vaccines [5,6] encoding Spike proteins have been approved for urgent use in China, the US, and other countries. These vaccines do not meet the need for vaccination in all countries. The inactivated COVID-19 vaccines are limited by manufacturing capacity due to difficulties in producing live viruses. The other major unanswered question is the duration of immune responses induced by the above vaccines

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