Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. 1). Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such sudden convergent evolution and its effect on humoral immunity remain unclear. Here we demonstrate that these convergent mutations can cause evasion of neutralizing antibody drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB and CH.1.1 are the most antibody-evasive strains tested. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies isolated from individuals who had BA.2 and BA.5 breakthrough infections2,3. Owing to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the neutralizing antibody binding sites and increased proportions of non-neutralizing antibody clones, which, in turn, focused humoral immune pressure and promoted convergent evolution in the RBD. Moreover, we show that the convergent RBD mutations could be accurately inferred by deep mutational scanning profiles4,5, and the evolution trends of BA.2.75 and BA.5 subvariants could be well foreseen through constructed convergent pseudovirus mutants. These results suggest that current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants. 

/pdf/imprinted-sars-cov-2-humoral-immunity-induces-convergent-2s5rkc2l.pdf

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

https://doi.org/10.1016/j.cell.2022.12.018

Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

https://www.nature.com/articles/s41591-022-01855-7.pdf

Modeling transmission of SARS-CoV-2 Omicron in China

http://www.cell.com/article/S0092867422004561/pdf

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

http://www.cell.com/article/S1931312822002207/pdf

Neutralization of SARS-CoV-2 Omicron sub-lineages BA.1, BA.1.1, and BA.2

Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines1,2. Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine. 

/pdf/memory-b-cell-repertoire-from-triple-vaccinees-against-lypmfchu.pdf

Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants

/pdf/memory-b-cell-repertoire-from-triple-vaccinees-against-1eg3tfzb.pdf

Yi-da Chen

Papers

Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants

Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants

Microstructure and properties of Al 2 O 3 -ZrO 2 composite coatings prepared by air plasma spraying