The latest achievement of Cao Yunlong's team: XBB.1.5 transmissibility enhancement is jointly promoted by strong binding of ACE2 and antibody escape, and neutralizing antibody SA55 still has strong activity against XBB.1.5

*For medical professionals only

Just now, the team of Cao Yunlong of Peking University published the latest research results on XBB.
1.
5 on the preprint platform bioRxiv [1].

This study results show that the enhanced transmissibility of XBB.
1.
5 is facilitated by strong binding to ACE2 and antibody escape
.
It is worth noting that the neutralizing antibody SA55 [2] screened by Xie Xiaoliang/Cao Yunlong's team, Xiao Junyu's team from Peking University School of Life Sciences, and Jin Ronghua's team from Beijing Ditan Hospital is still very effective
against XBB.
1.
5.

▲Screenshot of the first page of the paper

Recently, the number of people infected with the recombinant subtype XBB.
1.
5 of the new coronavirus has grown rapidly, quickly surpassing BQ.
1.
1 and other XBB subtypes
.
However, the mechanism of high transmissibility of XBB.
1.
5 remains unclear
.

In order to clarify the above problems, Cao's team evaluated the plasma neutralization titer
of XBB.
1.
5 in recovered patients based on pseudoviral neutralization experiments of vesicular stomatitis virus (VSV).
The plasma used in the study was derived from people who recovered from breakthrough infection (BTI) BA.
1, BA.
5 or BF.
7 after three doses of CoronaVac vaccine, and recovered from breakthrough infection BA.
5 after at least two doses of BNT162b2 or mRNA-1273 vaccine
.

Trends in the prevalence of different variants in the United States

The results of the study showed that compared with the B.
1 (D614G) variant, the plasma plasma of recovered patients with breakthrough infection BA.
5 after three doses of CoronaVac vaccine decreased by 44 times and NT50 for XBB.
1.
5 by 39 times; the plasma of recovered patients with breakthrough infection with BF.
7 decreased by 31 times for XBB.
1 and NT50 for XBB.
1.
5 decreased by 27 times
。 Similar trends
were shown in the plasma of people who recovered from breakthrough infection with BA.
5 after mRNA vaccination, and from patients who recovered from breakthrough infection with BA.
1 after three doses of CoronaVac vaccine.

The above results show that the humoral immune evasion ability of XBB.
1.
5 is comparable to that of XBB.
1, and is actually slightly weaker
.

▲Difference in neutralization titer of plasma of recovered patients

Yunlong's team also studied the escape ability
of XBB.
1.
5 against therapeutic neutralizing antibodies.

It was found that the neutralizing antibodies Evusheld and Bebtelovimab could not neutralize XBB.
1.
5 pseudovirus, S309 had weak activity against XBB.
1.
5 pseudovirus, and SA58 was also escaped, but SA55 was still very effective
against XBB.
1.
5 pseudovirus.

▲Escape of neutralizing antibodies

At the end of the study, they tested the affinity
of XBB.
1.
5 with human ACE2 (hACE2) using surface plasmon resonance (SPR) technology.

The results show that the binding affinity of RBD and hACE2 of XBB.
1.
5 (dissociation constant KD is 3.
4 nM) is comparable to BA.
2.
75 (KD=1.
8nM), but much stronger than XBB.
1 (KD=19nM) and BQ.
1.
1 (KD=8.
1nM
).

▲Comparison of affinity with hACE2

Previous studies have found that XBB.
1.
5 has an additional Ser486Pro mutation
in the S protein compared to the XBB.
1 variant.
Based on the above research results, Cao Yunlong's team believes that XBB.
1.
5 has a significant growth advantage over XBB.
1 for two reasons: first, XBB.
1.
5 greatly improves the affinity for binding to ACE2 through the Ser486Pro mutation; second, XBB.
1.
5 retains a very high immune escape ability
.

In addition, Cao's team also pointed out that the impact of increased affinity between XBB.
1.
5 and ACE2 on its pathogenicity needs to be studied as soon as possible, as well as the development of effective neutralizing antibodies and vaccines
against XBB.
1.
5.

It is understood that the pair of neutralizing antibodies SA55/SA58 has been transferred to Sinovac, China, and related clinical research is advancing [3].

References:

[1].
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The author of this article BioTalker