Robust neutralization of SARS-CoV-2 variants including JN.1 and BA.2.87.1 by trivalent XBB vaccine-induced antibodies

Abstract

The rapid and widespread transmission of SARS-CoV-2 has led to the emergence of multiple variants of concern (VOCs), most notably the Omicron variant, which continues to evolve and diversify into a range of sub-lineages. Our previous research has shown that these Omicron sub-lineages, spanning BA.1–BA.2.86, have been evolving to exhibit increased neutralization escape capabilities. 1 , 2 , 3 , 4 Since November 2023, the JN.1 variant, stemming from BA.2.86’s antigenic diversity and acquiring an additional mutation (L455S) in RBD, has rapidly emerged as the dominant strain. Additionally, a newly identified, highly mutated SARS-CoV-2 variant, BA.2.87.1, was detected in South Africa between September and November 2023, which has recently been classified as a variant under monitoring (VUM) and has sparked global concern. While it originates from the ancestral BA.2 lineage, BA.2.87.1 is genetically distinct from the currently circulating Omicron lineages. It exhibits over 100 mutations, with more than 30 in the spike protein, including notable changes in the receptor binding domain (RBD) like K417T, K444N, V445G, and L452M, which are crucial for antibody recognition. Intriguingly, this variant has 7 fragment deletions, including 3 in the spike protein, with 2 of which encompass over 10 crucial amino acids (Del 15–26 and Del 136–146) in the N-terminal domain (NTD) (Fig. 1a ). This evolutionary strategy, which involves sacrificing parts of the virus to evade the immune system, makes these deletions potentially more significant than nonsynonymous mutations. Given our existing immunity from vaccinations and past infection, the effectiveness of this immunity against BA.2.87.1 remains to be determined. Fig. 1 Neutralization of distinct SARS-CoV-2 sub-lineages by XBB reinfection and WSK-V102C vaccination sera. a The mutation frequency heatmap of BA.2.87.1 and other related lineages. Only mutations with a frequency higher than 0.75 are shown. Deletions are shown in cyan. Mutation frequency data was retrieved from the outbreak.info website. b Neutralization of different SARS-CoV-2 variant PsVs by sera collected from two groups of individuals who had previously experienced BA.5/BF.7 breakthrough infections following three doses of inactivated vaccines: one group were reinfection with XBB virus, the other group were boosted with the WSK-V102C vaccine. c In parallel comparison of neutralization GMTs against distinct Omicron subvariants by sera collected from individuals with XBB reinfection or with WSK-V102C booster vaccinations. d Neutralization of PsVs representing BA.2.87.1’s single and combined NTD deletions by sera collected from individuals with XBB reinfection or with WSK-V102C booster vaccination. Values above the symbols denote GMTs and their fold increase or decrease relative to WT (for panel b ) or BA.2 (for panel d ). Dotted lines indicate the threshold of detection (40 for all the cohorts). P values were determined by using multiple Mann–Whitney tests. WT wild-type Full size image

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