Polymorphism and Selection Pressure of SARS-CoV-2 Vaccine and Diagnostic Antigens: Implications for Immune Evasion and Serologic Diagnostic Performance.

Eric Dumonteil,Claudia Herrera

doi:10.3390/pathogens9070584

Abstract

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6–7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well-conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.

Highlights

The emergence and rapid spread of a novel Coronavirus, referred to as SARS-CoV-2, is resulting in one of the worst pandemics in the world, causing an unprecedented health and economic crisis.About seven months after the first cases were identified, over 8 million cases have been reported worldwide, with over 400,000 deaths according to the Johns Hopkins Coronavirus Resource Center [1].The pandemic has triggered multiple efforts at developing serological tests, able to detect both acute infections by detecting virus-specific IgM, as well as recovered individuals by detecting virus-specificIgG
For the N protein, we included a dataset of 16,656 sequences, and significant sequence diversity was detected, with up to 326 distinct protein sequences
It is of key importance to consider these aspects for serological test and vaccine development, to ensure their usefulness and broad efficacy

Summary

Introduction

The emergence and rapid spread of a novel Coronavirus, referred to as SARS-CoV-2, is resulting in one of the worst pandemics in the world, causing an unprecedented health and economic crisis.About seven months after the first cases were identified, over 8 million cases have been reported worldwide, with over 400,000 deaths according to the Johns Hopkins Coronavirus Resource Center [1].The pandemic has triggered multiple efforts at developing serological tests, able to detect both acute infections by detecting virus-specific IgM, as well as recovered individuals by detecting virus-specificIgG. Several immunochromatographic rapid tests are already available [2], and several more are likely to become available by the end of 2020. Such tools will be critical to increase testing for the accurate and rapid identification of cases and their isolation to limit further transmission of the virus. Their performance needs to be evaluated, and initial testing suggested variable performance of these tests [2,3].

Methods

Results

Conclusion