SARS-CoV-2 variant B.1.617 is resistant to bamlanivimab and evades antibodies induced by infection and vaccination

Abstract

The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply and a SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. Therefore, we analyze whether B.1.617 is more adept in entering cells and/or evades antibody responses. B.1.617 enters two out of eight cell lines tested with roughly 50% increased efficiency and is equally inhibited by two entry inhibitors. In contrast, B.1.617 is resistant against Bamlanivimab, an antibody used for COVID-19 treatment. B.1.617 evades antibodies induced by infection or vaccination, although less so than the B.1.351 variant. Collectively, our study reveals that antibody evasion of B.1.617 may contribute to the rapid spread of this variant.

Reduced neutralization of SARS-CoV-2 B.1.617 variant by inactivated and RBD-subunit vaccine

“…Our data indicated that B.1.617 variant Spike promotes virus infectivity through enhanced viral entry and membrane fusion, which may play an important role in increased transmissibility of this variant. These findings are highly consistent with previous studies 20 . L452R mutation in the RBD was reported to increase SARS-CoV-2 infectivity and fusogenicity 21 .…”

Effect of SARS-CoV-2 Mutations on the Efficacy of Antibody Therapy and Response to Vaccines

“…Neutralization titers were found to be lower in all relative to the WT; B.1.617.1 was 6.8 times less susceptible to neutralization by convalescent and vaccinee sera [ 49 ]. Another study evaluating the degree of inhibition of S protein–ACE 2 interaction and subsequent cell entry by convalescent sera from intensive care unit patients revealed a twofold reduction in inhibition relative to the WT; by comparison, the delta variant showed a sixfold decrease [ 50 ]. Additionally, delta showed a threefold reduction in inhibition by sera obtained from individuals who received the Pfizer-BioNTech vaccine compared to WT.…”

“…Additionally, delta showed a threefold reduction in inhibition by sera obtained from individuals who received the Pfizer-BioNTech vaccine compared to WT. In contrast, beta exhibited an elevenfold reduction [ 50 ]. Monotherapy with either mAb failed to inhibit virus-host cell interactions [ 43 , 50 ].…”

“…In contrast, beta exhibited an elevenfold reduction [ 50 ]. Monotherapy with either mAb failed to inhibit virus-host cell interactions [ 43 , 50 ]. However, bamlanivimab/etesevimab cocktail therapy has recently been reported to resolve symptoms in a severely ill patient infected with the delta variant [ 51 ].…”

Protective mucosal immunity against SARS-CoV-2 after heterologous systemic RNA-mucosal adenoviral vector immunization

“…Neutralization of various spike variants was assessed with the help of spike-pseudotyped simian immunodeficiency virus particles as described before 85 . For the production of pseudotyped reporter particles, HEK293T cells were transfected with the SIV-based self-inactivating vector encoding luciferase (pGAE-LucW), the SIV-based packaging plasmid (pAdSIV3), and the respective spike variantencoding plasmid [86][87][88] . For this purpose, 2x10 7 HEK293T cells were seeded the day before in a 175 cm 2 flask in Dulbecco's Modified Eagle's Medium (DMEM; Gibco) containing 10% FCS, 2 mM L-Glutamine, and 100 units/ml penicillin/streptomycin (D10 medium).…”