In a recent study published in the bioRxiv*preprint server, researchers conducted an epidemic dynamic analysis to assess the XBB.1.5 sub-VOC characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern (VOC).
Coronavirus disease 2019 (COVID-19) has caused unprecedented morbidity and mortality on a global scale. The efficacy of COVID-19 vaccines and other therapeutic agents, such as monoclonal antibodies, has been challenged by the continued emergence of SARS-CoV-2 variants with increased transmissibility, infectivity, immune evasiveness, and viral fitness.
The authors of the present study previously reported the virologic characteristics of several novel Omicron subCOVs. By December 2022, the sub-VOC Omicron XBB.1.5, derived from the sub-VOC XBB.1, the spike protein containing the F486P mutation, emerged and has been rapidly transmitting in the United States of America (USA). ) and other parts of the world. the globe ever since. More research is required to determine the virologic characteristics of newly emerging variants to inform policymaking and guide the development of updated vaccines to reduce the health burden of COVID-19.
About the study
The present study expanded on the researchers’ previous analysis by clarifying the characteristics of XBB.1.5.
Yeast surface visualization assays and pseudovirus assays were performed to assess the affinity of the soluble angiotensin converting enzyme 2 (ACE2) binding interaction and the infectivity of XBB.1.5. respectively. For pseudovirus assays, HOS cells stably expressing human ACE2 and transmembrane serine protease 2 (TMPRSS2) were infected with SARS-CoV-2 pseudoviruses comprising variant spike proteins. Viral entries were normalized based on amounts of HIV-1 (human immunodeficiency virus 1) p24 capsid protein.
In addition, SARS-CoV-2 neutralization assays were performed to assess resistance to Omicron BA.2 sub-VOC and Omicron BA.5 sub-VOC breakthrough infection (BTI) sera, using pseudoviruses comprising spike proteins. from strain B.1.1, strain BA.2, strain BA.5, strain BQ.1.1, strain XBB.1, strain XBB.1 lacking the S:Y144del (XBB.1+ins144Y) mutation, strain XBB. 1.5 and strain XBB.1.5 strain lacking the S:Y144del mutation (XBB.1.5+ins144Y).
Serum samples were obtained from 13 people convalescing from COVID-19 who had received full COVID-19 vaccinations and had a history of infection with Omicron BA.2 after full COVID-19 vaccination, of whom nine people had received two doses and four people had received three doses of vaccines against COVID-19.
In addition, sera were obtained from 20 convalescents from Omicron BA.5 infection, of which two individuals, 17 individuals, and one individual had received two doses, three doses, and four doses of COVID-19 vaccines, respectively. For all serum samples, the team performed assays in triplicate to determine the NTfifty (50 percent neutralization) titles. All virological characteristics evaluated were compared with those of the parent strain XBB.1. Bayesian analysis was performed using a 95 percent confidence interval (CI).
The estimated relative Re (effective reproductive number) of strain XBB.1.5 was >1.20-fold higher than that of the parental strain XBB.1, and strain XBB.1.5 outperformed strain BQ.1.1 which dominated in the USA in December. 2022. The finding indicated that the XBB.1.5 strain would be rapidly transmitted globally in the future.
The estimated infectivity and ACE2 binding affinities of the XBB.1.5 strain were three and four times higher than the corresponding properties of the XBB.1 strain, respectively. The findings indicated that the XBB.1.5 strain exhibited a markedly stronger ACE2 binding affinity due to the F486P mutation, while the 144Y mutation elevated the infectivity of the XBB.1 strain. The infectivity of the XBB.1.5 strain was not improved by the 144Y mutation.
Strain XBB.1.5 showed strong resistance to Omicron BA.2 BTI sera (41.0-fold against B.1.1 strain, 20.0-fold against Omicron BA.2 strain) and BA.5 BTI sera ( 32.0-fold against the B .1.1 strain, 10-fold against the Omicron BA.5 strain), respectively. The 144Y insertion mutation significantly improved the sensitivity of XBB.2.5 to Omicron BA.2 sub-VOC BTI and Omicron BA.5 sub-VOC BTI sera. The immunological resistance of the strain XBB.1.5 and the parental strain XBB.1 was comparable.
In addition, a part of the XBB.1.5 strain lost the S:Y144del mutation, which increases immune evasiveness but reduces infectivity. However, the XBB.1.5 strain lacking the S:Y144del mutation (XBB.1.5+ins144Y) exhibited a relatively lower effective reproductive number than the original XBB.1.5 strain.
Overall, the findings from the epidemic dynamics analysis showed that the new strain XBB.1.5 is the most successful XBB strain to date, comprising the F486P mutation in the spike protein, which enhanced the ACE2 receptor binding affinity without a marked loss in immune resistance, leading to increased transmissibility. .
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice or health-related behavior, or treated as established information.
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