Profound neutralization evasion and augmented host cell entry are hallmarks of the fast-spreading SARS-CoV-2 lineage XBB.1.5

Since late 2022, the share of infections caused by the SARS-CoV2 lineage XBB.1.5 has gradually increased in the United States,resulting in XBB.1.5 becoming the dominating SARS-CoV-2lineage in the United States and a similar trend is likely to soontake place also in European countries. However, information onthe virological properties of XBB.1.5 is scarce. Here, weconducted an initial virological assessment of the SARS-CoV-2XBB.1.5 lineage.

Host cell entry and neutralisation sensitivity of the SARS-CoV-2 XBB.1.16 lineage

Despite previous circulation of the highly transmissible and antibody evasive BA.2.75, BQ.1, XBB.1 and XBB.1.5 lineages, the share of infections caused by the SARS-CoV-2 lineage XBB.1.16 has gradually increased in India in early 2023, resulting in XBB.1.16 being the dominating SARS-CoV-2 lineage in India today. Since a similar trend may also take place in other countries and information on the biological properties of the XBB.1.16 lineage is scarce, we conducted a rapid assessment of the SARS-CoV-2 XBB.1.16 lineage with respect to its ability to enter cells and evade neutralisation by antibodies.

Delta variant(B.1.617.2)sublineages do not show increased neutralization resistance

The emergence of SARS-CoV-2 variants threatens efforts to control the COVID-19 pandemic.At present,the global spread of the Delta(B.1.617.2)variant is responsible for a rapid increase in COVID-19 cases and hospitalizations in many countries.The variant evades neutralizing antibodies and is believed to be more transmissible and pathogenic[1,2,3,4].

The spike protein of SARS-CoV-2 variant A.30 is heavily mutated and evades vaccine-induced antibodies with high efficiency

The COVID-19 pandemic,caused by SARS-CoV-2,continues to rage in many countries,straining health systems and economies.Vaccines protect against severe disease and death and are considered central to ending the pandemic.COVID-19 vaccines(and SARS-CoV-2 infection)elicit antibodies that are directed against the viral spike(S)protein and neutralize the virus.However,the emergence of SARS-CoV-2 variants with S protein mutations that confer resistance to neutralization might compromise vaccine efficacy[1].

No evidence for increased cell entry or antibody evasion by Delta sublineage AY.4.2

Since the beginning of the COVID-19 pandemic,multiple SARS-CoV-2 variants have emerged.While some variants spread only locally,others,referred to as variants of concern,disseminated globally and became drivers of the pandemic.All SARS-CoV-2 variants harbor mutations relative to the virus circulating early in the pandemic,and mutations in the viral spike(S)protein are considered of particular relevance since the S protein mediates host cell entry and constitutes the key target of the neutralizing antibody response.As a consequence,mutations in the S protein may increase SARS-CoV-2 infectivity and enable its evasion of neutralizing antibodies.Furthermore,mutations in the S protein can modulate viral transmissibility and pathogenicity.

Efficient antibody evasion but reduced ACE2 binding by the emerging SARS-CoV-2 variant B.1.640.2

The SARS-CoV-2 spike(S)protein engages ACE2 for cell entry,and the S protein/ACE2 interface is an important target for neutralizing antibodies.In the course of the COVID-19 pandemic,SARS-CoV-2 variants have emerged that harbor mutations in the S protein,which confer neutralization resistance and allow viral spread in immunologically nonnaive populations.The most prominent example is the highly mutated Omicron variant,which infects convalescent or vaccinated individuals with unprecedented efficiency[1,2].

Mutation D614G increases SARS-CoV-2 transmission

It has been unclear why SARS-CoV-2 with a D614G mutation in the spike protein became dominant early in the COVID-19 pandemic.A recent study by Hou et al.published in Science shows that D614G increases SARS-CoV-2 spread in cultured human nasal epithelium and enhances transmission in a hamster model.