Impact of SARS-CoV-2 variant-associated RBD mutations on the susceptibility to serum antibodies elicited by COVID-19 infection or vaccination

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

BACKGROUND: Several 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 COVID-19 patients or BNT162b2 vaccinees was determined using a live virus microneutralization (MN) assay. Serum 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 (3.4-5.7-fold lower) or individuals who have received 2 doses of BNT162b2 vaccine (4.4-7.3-fold lower). The GMT of B.1.351 or P.3 were lower than that of B.1.671.1. 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. CONCLUSION: P.3 and B.1.617.1 escape serum neutralization induced by natural infection or vaccine. Infection with one variant do not confer cross protection for heterologous lineages. Immunogenicity testing for second generation COVID-19 vaccines should include multiple variant and "non-variant" strains.