By Varun Anipindi

The Indian subcontinent is reeling from an unprecedented second wave of COVID-19 infections since March 2021. The country is facing an exponential increase in COVID-19 cases and deaths, and this is related to the emergence of a new variant, B.1.617, that was initially described in the state of Maharashtra. Since then, the variant has rapidly spread throughout the nation and has emerged in at least 40 other countries, including Canada.

 

Key points:

  • Specific mutations identified in the B.1.617 lineage are responsible for its increased viral transmission
  • The current portfolio of vaccines and anti-viral treatments are still effective (albeit at lower efficiency) to protect against this new variant

 

The novel B.1.617 variant harbors eight mutations in the Spike protein, including L452R and E484Q in the receptor binding domain (which critically interacts with the ACE2 target receptor expressed on a variety of human cells), and a P681R mutation which augments viral fusion with the host cell. Over the past few weeks, three pre-prints have been published to provide insights into the emergence and sensitivity of this variant to current antibody-based therapeutics and vaccines.

A pre-print published by Ferreira I. et al examines the evolution of the B.1.617 strain and provides insight on how these mutations may lead to increased transmission and enable infection in previously vaccinated individuals. The scientists characterized three lineages of this variant: B.1.617.1, B.1.617.2 and B.1.617.3, among which the first two are steadily increasing across India and the UK, respectively. Critically, surveillance of healthcare workers vaccinated with the AstraZeneca vaccine in New Delhi demonstrated that B.1.617.2 was associated with the infection of 30 previously vaccinated individuals during the second wave in March 2021. The researchers also suggested that the E484Q and L452R mutations may be the reason for the reduction in neutralization capacity of sera in vaccinated people. Finally, they also demonstrated that the addition of the P681R mutation induced a higher degree of viral fusion with host cells which might be associated with higher levels of transmission.

 

Ferreira I, Datir R, Kemp S, Papa G, Rakshit P, Singh S, Meng B, Pandey R, Ponnusamy K, Radhakrishnan VS, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, Sato K, James L, Agrawal A, Gupta RK. SARS-CoV-2 B.1.617 emergence and sensitivity to vaccine-elicited antibodies. bioRxiv. 2021 May 18. doi: 10.1101/2021.05.08.443253.

 

In another pre-print published by Hoffmann and colleagues, researchers reached a similar consensus for why B.1.617 may be leading to increased COVID-19 infections and deaths in India. They showed that this variant has an increased ability to enter cells and can infect a broader range of target cells, specifically those within the human intestines and lungs. That said, current therapeutics still appear to be effective at blocking viral entry. Inhibitors such as soluble ACE2 (which blocks the viral RBD) and Camostat (which prevents activation of the S protein) have been successful at blocking interaction of the viral RBD with ACE2 targets on the cell surface. However, two of the four currently approved monoclonal antibodies (Casirivimab and Bamblanivimab) were no longer suitable for blocking the B.1.617 variant. Finally, the authors demonstrated that this variant may, to a small degree, evade antibody-mediated control in COVID-19 convalescent patients, or antibodies induced by vaccination with the Pfizer-BioNTech mRNA based vaccine.

 

Hoffmann M, Hofmann-Winkler H, Krüger N, Kempf A, Nehlmeier I, Graichen L, Sidarovich A, Moldenhauer A-S, Winkler MS, Schulz S, Jäck H-M, Stankov MV, Behrens GMN, Pöhlmann S. SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination. bioRxiv. 2021 May 5. doi: 10.1101/2021.05.04.442663.

 

Finally, in a pre-print by Edara and colleagues, researchers use an in vitro neutralization assay to demonstrate that the B.1.617.1 variant may be 6.8-fold less susceptible to neutralization by antibodies found in COVID-19 convalescent sera or sera from people vaccinated with the Moderna or Pfizer-BioNTech mRNA vaccines.

 

Edara V-V, Lai L, Sahoo MK, Floyd K, Sibai M, Solis D, Flowers MW, Hussaini L, Ciric CR, Bechnack S, Stephens K, Mokhtari EB, Mudvari P, Creanga A, Pegu A, Derrien-Colemyn A, Henry AR, Gagne M, Graham BS, Wrammert J, Douek DC, Boritz E, Pinsky BA, Suthar MS. Infection and vaccine-induced neutralizing antibody responses to the SARS-CoV-2 B.1.617.1 variant. bioRxiv. 2021 May 10. doi: 10.1101/2021.05.09.443299