Abstract
The SARS-CoV-2 B.1.617 lineage variants, Kappa (B.1.617.1) and Delta (B.1.617.2, AY) emerged during the second wave of infections in India, but the Delta variants have become dominant worldwide and continue to evolve. Here, we compared B.1.617 variants for neutralization resistance by convalescent sera, mRNA vaccine-elicited sera, and therapeutic neutralizing antibodies using a pseudovirus neutralization assay. B.1.617.1, B.1.617.2, and AY.1 pseudoviruses showed a modest 1.5- to 4.4-fold reduction in neutralization by convalescent sera and vaccine-elicited sera. In comparison, similar modest reductions were also observed for C.37, P.1, R.1, and B.1.526 pseudoviruses, but 7- and 16-fold reductions for vaccine-elicited and convalescent sera, respectively, were seen for B.1.351 pseudoviruses. Among twenty-three therapeutic antibodies tested, four antibodies showed either complete or partial loss of neutralization against B.1.617.2 pseudoviruses and six antibodies showed either complete or partial loss of neutralization against B.1.617.1 and AY.1 pseudoviruses. Our results indicate that the current mRNA-based vaccines will likely remain effective in protecting against B.1.617 variants. Finally, the P681R substitution confers efficient cleavage of B.1.617 variants’ spike proteins and the spike of Delta variants exhibited greater sensitivity to soluble ACE2 neutralization, as well as fusogenic activity, which may contribute to enhanced spread of Delta variants.
Highlights
Since its origin in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally to cause a coronavirus disease 2019 (COVID-19) pandemic that recorded more than 263 million infections and has claimed 5.2 million lives far (Johns Hopkins Coronavirus Resource Center; https://coronavirus.jhu.edu, accessed date: 1 December 2021)
Because the convalescent sera came from individuals who were previously infected by different variants (Table 2), we explored differences in the neutralization titers between those infected by D614G variants lacking L452R and those infected by variants containing L452R
We show that pseudoviruses bearing B.1.617.1 spike with L452R and E484Q substitutions, and B.1.617.2 spike with K417N, L452R and T478K substitutions, have modestly reduced susceptibility to neutralization by Pfizer/BioNtech BNT162b2 or Moderna mRNA-1273 vaccine-elicited sera and convalescent sera compared to pseudoviruses bearing WT(D614G) spike
Summary
Since its origin in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally to cause a coronavirus disease 2019 (COVID-19) pandemic that recorded more than 263 million infections and has claimed 5.2 million lives far (Johns Hopkins Coronavirus Resource Center; https://coronavirus.jhu.edu, accessed date: 1 December 2021). SARS-CoV-2 trimeric spike (S) glycoprotein on the virion surface binds the angiotensin-converting enzyme (ACE2) to facilitate cellular entry and is the target of therapeutic neutralizing antibodies and vaccines [1,2,3,4,5,6]. Available vaccines and therapeutic antibodies target the spike glycoprotein of an early isolate of SARS-CoV-2. The continued evolution of SARS-CoV-2 resulted in the emergence of several variants of distinct lineages globally, raising concerns over variant transmissibility and immune escape. The Kappa (B.1.617.1) variant emerged early in the second wave, followed by the Delta (B.1.617.2) and its sublineage (AY. and AY.2) variants, which are currently dominant in many parts of the world
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