Jesse Bloom PRO
Scientist studying evolution of proteins and viruses.
Fred Hutch Cancer Research Center / HHMI
Slides at https://slides.com/jbloom/sars-cov-2-science-advisors
They might be more transmissible
They might be less recognized by immunity
They might be more transmissible
They might be less recognized by immunity
Bad, but we can't do much about it
They might be more transmissible
They might be less recognized by immunity
Bad, but we can't do much about it
Bad, and we can potentially update vaccine strategies, so I will focus on this.
We can address this question by studying historical evolution of other human coronaviruses.
We chose CoV-229E, which causes common colds and has circulated in humans since at least 1960s.
old virus (e.g., 1984)
old virus (e.g., 1984)
extent of virus neutralization
Measure how old serum neutralizes old virus
old virus (e.g., 1984)
extent of virus neutralization
Measure how old serum neutralizes newer virus
newer viruses
measles-like
influenza-like
We experimentally generated CoV-229E spikes at ~8 year intervals so we could study them in the lab:
- 1984
- 1992
- 2001
- 2008
- 2016
We are studying basis of these differences, as ideally vaccines would elicit more evolution-resistant sera as on the right.
Plot of sequence variability across CoV-229E spike taken from Eguia, ..., Bloom, PLoS Pathogens (2021) . See also Wong, ..., Rini, Nature Communications (2017) and Li, ..., Rini, eLife (2019) for detailed structural studies of evolution in receptor-binding loops.
Phylogenetic tree of 1,142,265 full-length SARS-CoV-2 genomes provided by GISAID
Phylogenetic tree of 1,142,265 full-length SARS-CoV-2 genomes provided by GISAID
RBD
fluorescently labeled antibody
yeast
fluorescent tag on RBD
Click here for details on how library is made.
In maps, tall letters indicate strong escape mutations
Interactive map of escape for LY-CoV555 (antibody in Eli Lilly's bamlanivimab)
S309 (VIR-7381)
Pre-print available here
Interactive maps and raw data available here
Studies validating these conclusions from the mapping:
lineage | LY-CoV555 | LY-CoV016 | REGN10933 | REGN10987 | COV2-2196 | COV2-2130 |
---|---|---|---|---|---|---|
B.1.1.7 20I/501Y.V1 (UK) |
none | none | none | none | none | none |
B.1.351 20H/501Y.V2 (S. Africa) |
E484K |
K417N E484K (partial) |
K417N (partial) E484K (partial) |
none | E484K (slight) | none |
P.1 20J/501Y.V3 (Brazil) |
E484K |
K417T E484K (partial) |
K417T (partial) E484K (partial) |
none | E484K (slight) | none |
B.1.429 20C/CAL.20C (USA/CA) |
L452R | none | none | none | none | none |
B.1.526 (USA/NY) |
E484K | E484K (partial) | E484K (partial) | none | E484K (slight) | none |
Monoclonal antibody can typically be escaped by a single viral mutation
Polyclonal antibodies bind many epitopes, so typically more resistant to evolutionary escape
frequency of mutations at site
(all sequences in GISAID)
frequency of mutations at site
(all sequences in GISAID)
Single worst mutation for antibody immunity is E484K, which typically reduces serum neutralization by 4- to 10-fold
Some viruses evolve to erode immunity (influenza), others do not (measles)
Some viruses evolve to erode immunity (influenza), others do not (measles)
Unfortunately, human coronaviruses do evolve to erode immunity
Some viruses evolve to erode immunity (influenza), others do not (measles)
Unfortunately, human coronaviruses do evolve to erode immunity
New SARS-CoV-2 variants contain mutations (eg, E484K, L452R, K417N) that partially erode antibody immunity
Some viruses evolve to erode immunity (influenza), others do not (measles)
Unfortunately, human coronaviruses do evolve to erode immunity
New SARS-CoV-2 variants contain mutations (eg, E484K, L452R, K417N) that partially erode antibody immunity
However, it will take multiple years (~3-5??) for SARS-CoV-2 to accumulate enough mutations to strongly evade polyclonal antibody neutralization
Some viruses evolve to erode immunity (influenza), others do not (measles)
Unfortunately, human coronaviruses do evolve to erode immunity
Therefore, we need to monitor impacts of viral evolution for possible vaccine updates.
New SARS-CoV-2 variants contain mutations (eg, E484K, L452R, K417N) that partially erode antibody immunity
However, it will take multiple years (~3-5??) for SARS-CoV-2 to accumulate enough mutations to strongly evade polyclonal antibody neutralization
Some viruses evolve to erode immunity (influenza), others do not (measles)
Unfortunately, human coronaviruses do evolve to erode immunity
Therefore, we need to monitor impacts of viral evolution for possible vaccine updates.
Also, it remains unclear whether disease will typically still be severe in re-infections
New SARS-CoV-2 variants contain mutations (eg, E484K, L452R, K417N) that partially erode antibody immunity
However, it will take multiple years (~3-5??) for SARS-CoV-2 to accumulate enough mutations to strongly evade polyclonal antibody neutralization
Crowe lab (Vanderbilt): James Crowe, Seth Zost, Pavlo Gilchuk
Chu lab (Univ Wash): Helen Chu, Caitlin Wolf
Veesler lab (Univ Wash): David Veesler, Alexandra Walls, Ale Tortorici
King lab (Univ Wash): Neil King, Dan Ellis
Li lab (Brigham & Women's): Jonathan Li, Manish Choudhary
Whelan lab (Wash U)
Boeckh lab (Fred Hutch): Terry Stevens-Ayers
Alex Greninger (Univ Wash)
Janet Englund (Seattle Children's)
These slides: https://slides.com/jbloom/sars-cov-2-science-advisors
Adam Dingens
Will Hannon
Amin Addetia
Keara Malone
Tyler Starr
Allie Greaney
Rachel Eguia
Bloom lab (Fred Hutch)
Sarah Hilton
Kate Crawford
Andrea Loes
By Jesse Bloom
SARS-CoV-2 evolution presentation for May 4 Chief Science Advisors Meeting
Scientist studying evolution of proteins and viruses.