Post by Nadica (She/Her) on Oct 23, 2024 1:22:17 GMT
Virological characteristics of the SARS-CoV-2 XEC variant - Preprint posted Oct 17, 2024
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Abstract
32 The SARS-CoV-2 JN.1 variant (BA.2.86.1.1), arising from BA.2.86.1 with spike
33 protein (S) substitution S:L455S, outcompeted the previously predominant XBB
34 lineages by the beginning of 2024. Subsequently, JN.1 subvariants including KP.2
35 (JN.1.11.1.2) and KP.3 (JN.1.11.1.3), which acquired additional S substitutions
36 (e.g., S:R346T, S:F456L, and S:Q493E), have emerged concurrently. As of
37 October 2024, KP.3.1.1 (JN.1.11.1.3.1.1), which acquired S:31del, outcompeted
38 other JN.1 subvariants including KP.2 and KP.3 and is the most predominant
39 SARS-CoV-2 variant in the world. Thereafter, XEC, a recombinant lineage of
40 KS.1.1 (JN.13.1.1.1) and KP.3.3 (JN.1.11.1.3.3), was first identified in Germany
41 on August 7, 2024. XEC acquired two S substitutions, S:T22N and S:F59S,
42 compared with KP.3 through recombination, with a breakpoint at genomic position
43 21,738–22,599. We estimated the relative effective reproduction number (Re) of
44 XEC using a Bayesian multinomial logistic model based on genome surveillance
45 data from the USA, the United Kingdom, France, Canada, and Germany, where
46 this variant has spread as of August 2024. In the USA, the Re of XEC is 1.13-fold
47 higher than that of KP.3.1.1. Additionally, the other countries under investigation
48 herein showed higher Re for XEC. These results suggest that XEC has the
49 potential to outcompete the other major lineage including KP.3.1.1. We then
50 assessed the virological properties of XEC using pseudoviruses. Pseudovirus
51 infection assay showed that the infectivity of KP.3.1.1 and XEC was significantly
52 higher than that of KP.3. Although S:T22N did not affect the infectivity of the
53 pseudovirus based on KP.3, S:F59S significantly increased it. Neutralization
54 assay was performed using three types of human sera: convalescent sera after
55 breakthrough infection (BTI) with XBB.1.5 or KP.3.3, and convalescent sera after
56 JN.1 infection. In all serum groups, XEC as well as KP.3.1.1 showed immune
57 resistance when compared to KP.3 with statistically significant differences. In the
58 cases of XBB.1.5 BTI sera and JN.1 infection sera, the 50% neutralization titers
59 (NT50s) of XEC and KP.3.1.1 were comparable. However, we revealed that the
60 NT50 of XEC was significantly (1.3-fold) lower than that of KP.3.1.1. Moreover,
61 both S:T22N and S:F59S significantly (1.5-fold and 1.6-fold) increased the
62 resistance to KP.3.3 BTI sera. Here we showed that XEC exhibited higher
63 pseudovirus infectivity and higher immune evasion than KP.3. Particularly, XEC
64 exhibited more robust immune resistance to KP.3.3 BTI sera than KP.3.1.1. Our
65 data suggest that the higher Re of XEC than KP.3.1.1 is attributed to this property
66 and XEC will be a predominant SARS-CoV-2 variant in the world in the near future.
Sorry, I do not have the time to reformat this right now.
Abstract
32 The SARS-CoV-2 JN.1 variant (BA.2.86.1.1), arising from BA.2.86.1 with spike
33 protein (S) substitution S:L455S, outcompeted the previously predominant XBB
34 lineages by the beginning of 2024. Subsequently, JN.1 subvariants including KP.2
35 (JN.1.11.1.2) and KP.3 (JN.1.11.1.3), which acquired additional S substitutions
36 (e.g., S:R346T, S:F456L, and S:Q493E), have emerged concurrently. As of
37 October 2024, KP.3.1.1 (JN.1.11.1.3.1.1), which acquired S:31del, outcompeted
38 other JN.1 subvariants including KP.2 and KP.3 and is the most predominant
39 SARS-CoV-2 variant in the world. Thereafter, XEC, a recombinant lineage of
40 KS.1.1 (JN.13.1.1.1) and KP.3.3 (JN.1.11.1.3.3), was first identified in Germany
41 on August 7, 2024. XEC acquired two S substitutions, S:T22N and S:F59S,
42 compared with KP.3 through recombination, with a breakpoint at genomic position
43 21,738–22,599. We estimated the relative effective reproduction number (Re) of
44 XEC using a Bayesian multinomial logistic model based on genome surveillance
45 data from the USA, the United Kingdom, France, Canada, and Germany, where
46 this variant has spread as of August 2024. In the USA, the Re of XEC is 1.13-fold
47 higher than that of KP.3.1.1. Additionally, the other countries under investigation
48 herein showed higher Re for XEC. These results suggest that XEC has the
49 potential to outcompete the other major lineage including KP.3.1.1. We then
50 assessed the virological properties of XEC using pseudoviruses. Pseudovirus
51 infection assay showed that the infectivity of KP.3.1.1 and XEC was significantly
52 higher than that of KP.3. Although S:T22N did not affect the infectivity of the
53 pseudovirus based on KP.3, S:F59S significantly increased it. Neutralization
54 assay was performed using three types of human sera: convalescent sera after
55 breakthrough infection (BTI) with XBB.1.5 or KP.3.3, and convalescent sera after
56 JN.1 infection. In all serum groups, XEC as well as KP.3.1.1 showed immune
57 resistance when compared to KP.3 with statistically significant differences. In the
58 cases of XBB.1.5 BTI sera and JN.1 infection sera, the 50% neutralization titers
59 (NT50s) of XEC and KP.3.1.1 were comparable. However, we revealed that the
60 NT50 of XEC was significantly (1.3-fold) lower than that of KP.3.1.1. Moreover,
61 both S:T22N and S:F59S significantly (1.5-fold and 1.6-fold) increased the
62 resistance to KP.3.3 BTI sera. Here we showed that XEC exhibited higher
63 pseudovirus infectivity and higher immune evasion than KP.3. Particularly, XEC
64 exhibited more robust immune resistance to KP.3.3 BTI sera than KP.3.1.1. Our
65 data suggest that the higher Re of XEC than KP.3.1.1 is attributed to this property
66 and XEC will be a predominant SARS-CoV-2 variant in the world in the near future.