Fig. 1.

Cross-variant neutralization of SARS-CoV-2 isolates and consideration for boosting the immune response to SARS-CoV-2 variants. a Mice were infected with 1 × 10⁴ p.f.u. of WA1, Delta, or Omicron. Unvaccinated or vaccinated individuals were infected with likely Delta or Omicron BA.1. The numbers in parentheses indicate the neutralization efficacy (NT50, 50% neutralization titer) of sera. The triple arrows indicate a higher neutralization activity against the indicated SARS-CoV-2 variants than the single arrow. The dash indicates no neutralization activity. The results suggest that the incorporation of Omicron-based immunogens in future multivalent/heterologous COVID-19 vaccination strategies may provide broader protection against VOCs. b Booster vaccination with WA.1 Spike has the potential to recruit previously-formed memory B cells, which undergo further affinity maturation through somatic hypermutations in their immunoglobulin genes. Omicron infection in those vaccinated individuals could reactivate those memory B cells that have sufficient affinity to recognize the variant despite many mutations in the RBD and spike. On the other hand, Omicron and WA.1 boost could, in theory, reactivate those memory B cells against more conserved epitopes as well as activate naive B cells specific for the Omicron spike. As the memory B cells have a pre-activated phenotype, they could respond more rapidly and outcompete naïve B cells, therefore the need to demonstrate new specificities derived from the naïve B cell response for a long period following the boost. The red cross indicates a B cell that do not recognize the Omicron variant but can be stimulated by the WA1 strain. MBCs Memory B cells, TfH T follicular Helper cells. The figure was generated using BioRender (https://biorender.com/)