Omicron's message on vaccines: Boosting begets breadth

Abstract

In this issue of Cell, three studies confirm that SARS-CoV-2 Omicron strongly evades a key immune defense-neutralizing antibodies. However, while one- or two-dose vaccine regimens fail to induce anti-Omicron neutralizing antibodies, a homologous third-dose booster rescues neutralization function in a way that highlights the adaptability of immune memory, where recalled immunity extends antibody reach across SARS-CoV-2 variants.

Figure 1

Homologous vaccine boosting and evolution of neutralizing breadth Schematic diagram of a hypothesized contributing mechanism underlying findings from three studies published in this issue of Cell (Dejnirattisai et al., 2022; Garcia-Beltran et al., 2021; Hoffmann et al., 2021), suggesting that homologous vaccine boosting enhances cross-variant antibody neutralization breadth. Naive (green) and early memory (blue) B cells produce an antibody pool of low maturity upon a two-dose vaccine regimen spaced 3–4 weeks apart. The early pool includes antibodies available from the baseline repertoire with high neutralization potency (dark red) to more variable regions of the SARS-CoV-2 viral spike protein. Through viral mutation and selection, the antibody pool size able to recognize it shrinks as the virus evolves in part to evade neutralization by antibodies (indicated by shrinking squares). The early antibody pool also includes relatively abundant antibodies with weak (orange) or no (yellow) neutralization potency to epitopic regions that do not change as much throughout viral evolution (i.e., more conserved epitopes). Antibody pools recognizing more conserved epitopes do not shrink as much with respect to evolving virus (indicated by relative maintenance of square size with respect to viral variant spikes). Because antibody affinity maturation can continue to occur in memory B cells over many months, a booster vaccine dose at 6 months would result in the production of higher-affinity versions of antibodies from these memory B cells. This may result in higher-potency neutralization function to the relatively abundant and more conserved regions of the spike protein.