The Dominant Omicron XBB1.5 Evades Antibodies and has Stronger ACE2 Binding

The XBB 5.1 is the most dominant SARS-CoV-2 Omicron subvariant in the US. According to the latest CDC COVID Data Tracker as of Dec 31, 2022, it causes 41% of COVID-19.[1]

Origin of the XBB

A study from Japan traced the origin of the XBB subvariant. It emerged after two co-circulating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), recombined in India during the summer of 2022.[2]

In vitro experiments revealed that XBB is “profoundly resistant” to antibodies developed against past BA.2 and BA.5 SARS-CoV-2 infections.

That means people who developed antibodies from Omicron BA.2 and BA.5  breakthrough infections can still get infected with the XBB.

BA.2 appeared in the US in March 2022, and BA.5 spread COVID-19 around July 2022. So, if you got COVID last year from these variants, you are not immune to XBB.

XBB also attaches more avidly to the ACE2 receptors of humans than the previous subvariant BA.2.75. This means greater infectiousness.

A related variant, the BA.2.75.2, evaded the immunity from the vaccines, and many antiviral drugs were ineffective against it.

Moreover, the study found that the XBB shows substantially higher viral fitness than its “parents.” Viral fitness is a term used to describe the ability of a viral variant to adapt and replicate competitively in a population of viruses.

The antibody resistance and greater ability to infect human cells explain why it is the prevailing SARS-CoV-2 infection in the US.

Resistant to Booster Shots and Monoclonal Antibodies

A Nov 2022 study from Columbia University and the University of Michigan in Ann Arbor showed that the XBB is immune to the antibodies produced by the WA1/BA.5 bivalent mRNA booster vaccine released last year.[3]

Compared to the ancestral D614G, an early SARS-CoV-2 that reached the US, the neutralizing antibody titers against the XBB are lower by 66-155-fold, much lower than other subvariants.

Additionally, 19 of 23 monoclonal antibodies lost neutralizing activity greatly against XBB and XBB.1.[3]

XBB.1.5

The third study is more specific to the XBB.1.5 subvariant. The authors are from Peking University and the Chinese Academy of Sciences. It was released yesterday.[4]

Compared to XBB.1, the XBB.1.5 has an additional Ser486Pro substitution [i.e., the amino acid serine (S) was replaced by proline (P) at position 486].

The study’s results echo the previous two, showing that XBB.1.5 exhibits a substantially higher binding to the ACE2 receptors than BQ.1.1 and XBB/XBB.1, making it more infectious. 

While the first study showed that the XBB is resistant to antibodies from previous BA.2 and BA.5 infections, XBB.1 and XBB.1.5 displayed evasion against antibodies from BA.1, BA.5, and BF.7 breakthrough infections and monoclonal antibodies.

The three studies are available as preprints from BioRxiv. They have not been peer-reviewed, but their findings are consistent.

Take away message

The XBB.1.5 is the most dominant SARS-CoV-2 now in the US. It is a severe threat due to its high infectiousness and ability to evade antibodies from previous vaccinations, breakthrough infections, and monoclonal antibodies.

Efforts should be made to minimize risk by improving the immune system and with early treatment.

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