Understanding the Secret of SARS-CoV-2 Variants of Concern/Interest and Immune Escape

Abstract

The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global public health. Four SARS-CoV-2 variants of concern including B.1.1.7, B.1.351, B.1.617.2, and P.1, and two variants of interest including C.37 and B.1.621 have been reported to have potential immune escape, and one or more mutations endow them with worrisome epidemiologic, immunologic, or pathogenic characteristics. This review introduces the latest research progress on SARS-CoV-2 variants of interest and concern, key mutation sites, and their effects on virus infectivity, mortality, and immune escape. Moreover, we compared the effects of various clinical SARS-CoV-2 vaccines and convalescent sera on epidemic variants, and evaluated the neutralizing capability of several antibodies on epidemic variants. In the end, SARS-CoV-2 evolution strategies in different transmission stages, the impact of different vaccination strategies on SARS-CoV-2 immune escape, antibody therapy strategies and COVID-19 epidemic control prospects are discussed. This review will provide a systematic and comprehensive understanding of the secret of SARS-CoV-2 variants of interest/concern and immune escape.

Keywords: SARS-CoV-2 variants; immune escape; neutralizing antibody; vaccine; variants of concern; variants of interest.

Figure 1

Brief information of four VOC variants. Four VOC variants (B.1.1.7, B.1.351, P.1, and B.1.617.2) are marked in the arrow according to the date of designation, and their related brief information (e.g., the time and location of earliest documented samples, infectivity, main mutations, immune escape ability) are displayed in the corresponding location.

Figure 2

Mutations of four VOC variants. Schematic showing the locations of amino acid substitutions of four VOCs (B.1.1.7, B.1.351, P.1, and B.1.617.2) in spike protein. The RBD region is shown in modena, the NTD region is shown in shallow orange.

Figure 3

Brief information of two VOI variants. Two VOI variants (C.37 and B.1.621) are marked in the arrow according to the date of designation, and their related brief information (e.g., the time and location of earliest documented samples, infectivity, main mutations, immune escape ability) are displayed in the corresponding location.

Figure 4

Mutations of two VOI variants. Schematic showing the locations of amino acid substitutions of two VOI variants (C.37 and B.1.621) in spike protein. The RBD region is shown in modena, the NTD region is shown in shallow orange.

Figure 5

Cross neutralization of convalescent plasma. The cross neutralization of convalescent serum has been noticed by the neutralization activity test. The convalescent serum from B.1.351-infected patients retained the neutralization against the virus in the first-wave epidemic in South Africa. However, the serum obtained from the first-wave of epidemic infection could not effectively neutralize B.1.351. The green arrow indicates that the neutralization still remains, and the light green means a worse neutralization effect. Pink indicates a significant decrease in neutralization efficacy.

Figure 6

Classification of neutralizing antibody targeting RBD. The neutralizing antibodies targeting SARS-CoV-2 RBD can be classified into four categories: (1) block ACE2 and bind only to ‘up’ RBDs; (2) block ACE2 and can bind to both ‘up’ and ‘down’ RBDs and can contact adjacent RBDs; (3) bind outside the ACE2 sites and recognize both ‘up’ and ‘down’ RBDs; (4) bind to the external residue sites of ACE2 and bind only to ‘up’ RBDs.