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. 2022 May 3;74(9):1623-1630.
doi: 10.1093/cid/ciab656.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination

Lin-Lei Chen  1 , Lu Lu  1 , Charlotte Yee-Ki Choi  1 , Jian-Piao Cai  1 , Hoi-Wah Tsoi  1 , Allen Wing-Ho Chu  1 , Jonathan Daniel Ip  1 , Wan-Mui Chan  1 , Ricky Ruiqi Zhang  1 , Xiaojuan Zhang  1 , Anthony Raymond Tam  2 , Daphne Pui-Ling Lau  3 , Wing-Kin To  4 , Tak-Lun Que  5 , Cyril Chik-Yan Yip  6 , Kwok-Hung Chan  1 , Vincent Chi-Chung Cheng  6 , Kwok-Yung Yuen  1   6 , Ivan Fan-Ngai Hung  2   7 , Kelvin Kai-Wang To  1   6
Affiliations

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant-Associated Receptor Binding Domain (RBD) Mutations on the Susceptibility to Serum Antibodies Elicited by Coronavirus Disease 2019 (COVID-19) Infection or Vaccination

Lin-Lei Chen et al. Clin Infect Dis. .

Abstract

Background: Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages with mutations at the spike protein receptor binding domain (RBD) have reduced susceptibility to antibody neutralization, and have been classified as variants of concern (VOCs) or variants of interest (VOIs). Here we systematically compared the neutralization susceptibility and RBD binding of different VOCs/VOIs, including B.1.617.1 (kappa variant) and P.3 (theta variant), which were first detected in India and the Philippines, respectively.

Methods: The neutralization susceptibility of the VOCs/VOIs (B.1.351, B.1.617.1, and P.3) and a non-VOC/VOI without RBD mutations (B.1.36.27) to convalescent sera from coronavirus disease 2019 (COVID-19) patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum immunoglobulin G (IgG) binding to wild-type and mutant RBDs were determined using an enzyme immunoassay.

Results: The geometric mean neutralization titers (GMT) of B.1.351, P.3, and B.1.617.1 were significantly lower than that of B.1.36.27 for COVID-19 patients infected with non-VOCs/VOIs (3.4- to 5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4- to 7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.617.1. For the 4 patients infected with B.1.351 or B.1.617.1, the MN titer was highest for their respective lineage. RBD with E484K or E484Q mutation, either alone or in combination with other mutations, showed greatest reduction in serum IgG binding.

Conclusions: P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with 1 variant does not confer cross-protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and "nonvariant" strains.

Keywords: COVID-19 vaccine; neutralization; receptor binding domain; reinfection; variant of concern.

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