COVID-19: analysis of the sensitivity of the Indian variant (B.1.617.2) to monoclonal antibodies and sera from convalescent and vaccinated individuals

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The variant known as the "Indian variant" (B.1.617) was detected for the first time in India in October 2020 and has since spread to several other countries, including the United Kingdom. In just a few months, the variant evolved into three subtypes, referred to as B.1.617.1, B.1.617.2 and B.1.617.3. Variant B.1.617.2, also termed variant Delta, is now dominant in some Indian regions and seems to be more transmissible than the others. Scientists from the Institut Pasteur, in collaboration with Georges Pompidou European Hospital (part of the Paris Public Hospital Network or AP-HP), Orléans Regional Hospital and Strasbourg University Hospital, studied the sensitivity of variant B.1.617.2 to monoclonal antibodies used in clinical practice to prevent severe forms of the disease in people at risk, as well as to neutralizing antibodies in the sera of individuals previously infected with SARS-CoV-2 or vaccinated. They compared this sensitivity with that of the dominant virus circulating in France (known as the "British variant", B.1.1.7, or variant Alpha) and the "South African variant" (B.1.351, or variant beta). The scientists demonstrated that the Delta variant is less sensitive to neutralizing antibodies than B.1.1.7. Three of the four therapeutic monoclonal antibodies tested are effective against the Indian variant, but one antibody (Bamlanivimab) loses its antiviral activity. The scientists demonstrated that sera from convalescent patients collected up to 12 months post symptoms were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. They also studied sera from people vaccinated with two doses of the Pfizer vaccine: their sera were effective against the British variant but slightly less effective against the Indian variant. Sera from individuals vaccinated with one dose of the AstraZeneca vaccine, was barely active against the Indian and South African variants. The study was published as a preprint on the bioRxiv website on May 28, 2021.

Since early 2021, India has been grappling with a steep increase in COVID-19 cases. Many of the cases have been caused by a new lineage, known as B.1.617. This lineage is constantly evolving and contains three main subtypes: B.1.617.1, B.1.617.2 and B.1.617.3. Our knowledge of the epidemiological and biological characteristics of these variants is still relatively poor. Variant B.1.617.2, characterized by nine mutations in the spike protein, seems to be particularly worrying and has been labeled as a "variant of concern" by several public health organizations, including WHO. It represents up to 80% of the strains sequenced in the state of Maharashtra in India. B.1.617.2 has also recently been detected in dozens of other countries.

In the United Kingdom, between May 12 and 19, 2021, the variant represented several thousand cases and more than 20% of virus strains sequenced. The number of cases of B.1.617.2 detected in the UK increased in the space of a few weeks, especially in London and in the north-west of the country, where it is now believed to represent 50% of sequenced cases. Most cases are imported from India, but a rise in the number of indigenous cases has been observed since mid-April.

In France, as of May 18, 2021, 80 confirmed cases involving a variant of the B.1.617 lineage had been reported.

In a new study, scientists from the Institut Pasteur, in collaboration with Hôpital Européen Georges Pompidou (part of the Paris Public Hospital Network or AP-HP), Orléans Regional Hospital and Strasbourg University Hospital, examined the sensitivity of variant B.1.617.2 to antibodies compared with the strains circulating in France and other variants (the British and South African variants). The aim of the study was to characterize the efficacy of therapeutic antibodies, as well as antibodies developed by individuals previously infected with SARS-CoV-2 or vaccinated, to neutralize this new variant.

The scientists isolated variant B.1.617.2 of SARS-CoV-2 from a nasal sample of a patient who developed COVID-19 a few days after returning from India. Therapeutic monoclonal antibodies and serum samples from people who had been vaccinated or previously exposed to SARS-CoV-2 were used to study the sensitivity of the variant to neutralizing antibodies.

"We isolated an infectious strain of virus B.1.617.2 and used a novel semi-automated rapid neutralization assay developed in our laboratory. This collaborative multidisciplinary effort involved the Institut Pasteur's virologists and specialists in the analysis of viral evolution and protein structure, together with teams from Hôpital Européen Georges Pompidou and the hospitals in Orléans and Strasbourg. We demonstrated that this variant, which spreads more rapidly, has acquired partial resistance to antibodies. For example, the sera of patients previously infected with COVID-19, collected up to 12 months after they experienced symptoms, and of individuals vaccinated with the Pfizer vaccine are still neutralizing but are three to six times less potent against B.1.617.2 as compared with B.1.1.7. And the sera of individuals vaccinated with a single dose of AstraZeneca Vaxzevria are relatively or completely ineffective against B.1.617.2," continues Olivier Schwartz, co-last author of the study and Head of the Virus and Immunity Unit at the Institut Pasteur.

The scientists also demonstrated that one therapeutic antibody, Bamlanivimab, no longer functions against this strain, although Etesevimab, Casirivimab and Imdevimab remain active.

The scientists concluded that the mutations in the spike protein of variant B.1.617.2 potentially modify virus binding to the receptor and allow partial escape from the immune response.



Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals. BioRxiv, May 28th 2021

Delphine Planas1,2, David Veyer3,4, Artem Baidaliuk5, Isabelle Staropoli1, Florence Guivel-Benhassine1, Maaran Michael Rajah1,6, Cyril Planchais7, Françoise Porrot1, Nicolas Robillard4, Julien Puech4, Matthieu Prot5, Floriane Gallais8,9, Pierre Gantner8,9, Aurélie Velay8,9, Julien Le Guen10, Najibi Kassis-Chikhani11, Dhiaeddine Edriss4, Laurent Belec4, Aymeric Seve12, Hélène Péré3, Laura Courtellemont12, Laurent Hocqueloux12, Samira Fafi-Kremer8,9, Thierry Prazuck12, Hugo Mouquet7, Timothée Bruel1,2**, Etienne Simon-Lorière5**, Felix A. Rey13**, Olivier Schwartz1,2**.

1Virus & Immunity Unit, Department of Virology, Institut Pasteur; CNRS UMR 3569, Paris, France

2Vaccine Research Institute, Creteil, France

3INSERM, Functional Genomics of Solid Tumors (FunGeST), Centre de Recherche des Cordeliers, Université de Paris and Sorbonne Université, Paris, France 

4Hôpital Européen Georges Pompidou, Laboratoire de Virologie, Service de Microbiologie, Paris, France 

5G5 Evolutionary genomics of RNA viruses, Department of Virology, Institut Pasteur, Paris, France

6Université de Paris, Sorbonne Paris Cité, Paris, France 

7Laboratory of Humoral Immunology, Department of Immunology, Institut Pasteur, INSERM U1222, Paris, France

8CHU de Strasbourg, Laboratoire de Virologie, Strasbourg, France 

9Université de Strasbourg, INSERM, IRM UMR_S 1109, Strasbourg, France 

10Hôpital Européen Georges Pompidou, Service de Gériatrie, Assistance Publique des Hôpitaux de Paris, Paris, France

11Hôpital européen Georges Pompidou, Unité d'Hygiène Hospitalière, Service de Microbiologie, Assistance Publique-Hôpitaux de Paris, Paris, 75015, France

12CHR d’Orléans, service de maladies infectieuses, Orléans, France

13Structural Virology Unit, Department of Virology, Institut Pasteur; CNRS UMR 3569, Paris, France

** co-last authors




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