02 COVID Thornburg 508

CDC ACIP — Vaccine Advisory Committee

Acip

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Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
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Current landscape of SARS -CoV-2 lineages
September 2023
Natalie J. Thornburg, PhD
Chief, Laboratory Branch
Coronaviruses and Other Respiratory Viruses Division
Trends in weighted lineage proportion estimates & Nowcast 
United States, May 27 –September 2, 2023
https://covid.cdc.gov/covid -data-tracker/#variant -proportions Accessed 9/1/2023
Two-week period ending
Convergent Evolution of Different Omicron Sub -lineages:
Key changes in the spike receptor binding domain (RBD) detected since September 2022
LineageSpike RBD (residues 333 -527) amino acid substitutions
339
§346
§,¶368 444
§,¶445
¶446
§,¶452
§,¶460
§,¶478 486
§,¶490
§,¶521
Reference sequence: BA.4/BA.5 D R L K V G R N K V F P
BA.4.6, BA.5.2.6, BF.7, BF.11 — T——————————
BQ.1 ——— T——— K————
BQ.1.1 — T— T——— K————
BA.2.75 H———— S L K— F——
BN.1 H T——— S L K— F S—
CH.1.1 H T— T— S— K— S——
XBB, XBB.1 H T I— P S L K— S S—
XBB.1.5, XBB.1.5.1, FD.2, XBB.1.9.1, 
XBB.1.9.2H T I— P S L K— P S—
XBB.1.16, XBB.1.16.1 H T I— P S L K R P S—
XBB.2.3 H T I— P S L K— P S S
Ma et al. MMWR to be published on June 15, 2023
§Indicates sites of independent substitutions in at least two different evolutionary lineages.
¶Indicates sites identified in a previous study associated with in vitro reductions in binding by monoclonal antibodies that were previously FDA -authorized.
Bolded sub -lineages are expanding in the United States as of June 10, 2023
More than 90% of circulating viruses have similar Spike receptor 
binding domain sequences
LineageSpike RBD (residues 333 -527) amino acid substitutions
452 455 456 460 478 486 521
Reference sequence: XBB.1.5 L L F K K P P
XBB.1.9 — — — — — S —
XBB.1.5.70 — F L — — — —
XBB.1.16 — — — — R — —
EG, FL — — L — — — —
EG.5 , EG.5.1.6 , FL.1.5 — — L — — — —
XBB.1.16.6, XBB.1.16.9, FL.1.5.1, HN.1 — — L — R — —
HV.1 R — L — — — —
HK.3 — F L — — — —
XBB.2.3 — — — — — — S
XBB.1.16, XBB.1.16.1 — — — — R — —
XBB.1.5 and XBB.1.16 Spike substitutions relative to 
BA.5
Receptor 
binding motif
Receptor 
binding domain
N-terminal 
domain
Remainder of 
S1
S2ACE2
ACE2XBB.1.5 XBB.1.16
BA.2.86 is a descendent of BA.2
Nexstrain (Roemer / Neher )•Most closely related 
to BA.2
•BA.2 and its lineages 
circulated in spring 
2022 before BA.5 
viruses

BA.2.86 has >30 amino acid substitions in spike in 
comparison to XBB.1.5
▪>30 amino acid substitutions in Spike in comparison to XBB.1.5
–Variation between sequences due to missing data and sequencing artifacts
▪First detected in specimen collected in late July, 2023
▪As of 9/6 detected in 7 clinical specimens in 7 US states and 1 additional state in 
waste water
▪Detected in 10 countries
▪Small number of sequences 

Reduction in pseudovirus neutralization is not detected 
using sera from people infected with XBB lineage 
viruses
Qian Wang 
Dr. David D. Ho lab

No reduction in BA.2.86 pseudovirus neutralization 
is observed after bivalent vaccination, or after 6 
months with or without XBB infection
Lasrado et al. Neutralization Escape by SARS -CoV-2 Omicron Subvariant BA.2.86 | bioRxiv

Data generation with authentic viruses
▪More than 90% of currently circulating viruses are XBB lineage viruses with 1 -2 
additional substitutions in RBD in comparison to XBB.1.5
▪BA.2.86 is a newly detected lineage with > 30 amino acid substitutions in spike
–Thus far, the number of viruses detected is still low
–Sequence numbers are too low to calculate proportion (<0.05%)
▪Preliminary pseudovirus neutralization data generated by multiple labs do not 
indicate a large reduction in neutralizing activity against BA.2.86
▪CDC has generated a BA.2.86 isolates, is currently working on titrations before 
neutralization and will distribute to external laboratories for further examination
▪More than 90% of currently circulating viruses are XBB lineage viruses with 1 -2 
additional substitutions in RBD in comparison to XBB.1.5
▪BA.2.86 is a newly detected lineage with > 30 amino acid substitutions in spike
–Thus far, the number of viruses detected is still low
–Sequence numbers are too low to calculate proportion (<0.05%)
▪Preliminary pseudovirus neutralization data generated by multiple labs do not 
indicate a large reduction in neutralizing activity against BA.2.86
▪CDC has generated a BA.2.86 isolate, is currently working on titrations before 
neutralization and has begun distribution to external laboratories for further 
examinationSummary
For more information, contact CDC
1-800 -CDC -INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official 
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation 
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.