Possible future evolution of XBB SARS-CoV-2 variants
Jesse Bloom
Fred Hutch Cancer Center / HHMI
These slides at https://slides.com/jbloom/future-sars2-escape-xbb
Recap of basic principles of human coronavirus evolution
SARS-CoV-2 imprinting and antibody responses
Possible future evolutionary steps in XBB
Recap of basic principles of human coronavirus evolution
SARS-CoV-2 imprinting and antibody responses
Possible future evolutionary steps in XBB
Other human CoVs cause annual waves
- Seasonal waves starting late Oct / early Nov, peaking Jan to mid Feb
- Often only one each of the alpha- and beta-coronaviruses cause large wave
Human CoV spikes evolve to escape neutralizing antibodies
Human sera from 1985-1990 neutralizes contemporaneous CoV-229E spikes quite well, but as virus evolves into the "future", neutralization is eroded. There is substantial heterogeneity in the rate of erosion across sera from different human individuals.
Antibody selection concentrated in RBD
Sites of evolutionary change in spike of CoV-229E over last four decades
Sites of mutations in SARS-CoV-2 Omicron BQ.1.1 spike relative to Wuhan-Hu-1
RBD does not run out of evolutionary space
25 of 31 residues in CoV-229E RBD that contact receptor varied during that virus's evolution in humans over last ~50 years (Li et al, 2019)
Recap of basic principles of human coronavirus evolution
SARS-CoV-2 imprinting and antibody responses
Possible future evolutionary steps in XBB
Imprinting: even after Omicron infection, neutralization highest against early strain
Imprinting: Omicron infection mostly boosts pre-existing B-cells to old strain
Omicron specific antibodies
Wu cross-reactive antibodies
But in Chinese cohort, two Omicron infections mostly breaks imprinting
Omicron specific antibodies
Wu cross-reactive antibodies
Immunological imprinting and CoV-229E?
People imprinted with first CoV-229E they are infected by, but still generally neutralize later strains to which they are exposed. Blue shading shows timeframe each individual alive prior to serum collection.
Recap of basic principles of human coronavirus evolution
SARS-CoV-2 imprinting and antibody responses
Possible future evolutionary steps in XBB
From Yunlong Cao, we have deep mutational scanning data on ~1000s antibodies that neutralize XBB
Sites of escape in XBB
Interactive escape calculator: https://jbloomlab.github.io/SARS2-RBD-escape-calc/
ACE2 affinity from: https://jbloomlab.github.io/SARS-CoV-2-RBD_DMS_Omicron/RBD-heatmaps/
Fitness effects from: https://jbloomlab.github.io/SARS2-mut-fitness/S.html
Interactive escape calculator: https://jbloomlab.github.io/SARS2-RBD-escape-calc/
Clear differences between one and two Omicron infections: eg, site 498 only major site of escape after two Omicron infections
We will probably see viral evolution at many of these sites of escape
See here for summary of how deep mutational scanning has predicted many of sites of antigenic evolution in the SARS-CoV-2 RBD over last few years