Scientists analyze the sensitivity of SARS-CoV-2 Delta variant to monoclonal antibodies

The Delta variant was detected for the first time in India in October 2020 and has since spread throughout the world. It is now dominant in many countries and regions (India, the UK, Portugal, Russia, etc.) and is predicted to be the most prevalent variant in Europe within weeks or months. Epidemiological studies have shown that the Delta variant is more transmissible than other variants.

Scientists from the Institut Pasteur (CNRS joint unit), in collaboration with Hôpital Européen Georges Pompidou (part of the Paris Public Hospital Network or AP-HP), Orléans Regional Hospital and Strasbourg University Hospital, studied the sensitivity of the Delta variant 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 virus previously circulating in France (known as the Alpha or "British variant") and the "South African variant" (Beta variant). The scientists demonstrated that the Delta variant is less sensitive to neutralizing antibodies than the Alpha variant. Three of the four therapeutic monoclonal antibodies tested are effective against the Delta variant, but one of them (Bamlanivimab) loses its antiviral activity.

The scientists demonstrated that sera from convalescent patients collected up to 12 months post symptoms were 4 fold less potent against the Delta variant, relative to the Alpha variant. They also studied sera from people vaccinated with two doses of the Pfizer or AstraZeneca vaccine: their sera effectively neutralized the Delta variant, although efficacy was slightly lower than against the Alpha variant. Sera from individuals who had received a single dose of vaccine (Pfizer or AstraZeneca) were inactive or barely active against the Delta and Beta variants. In summary, the Delta variant is slightly more resistant to neutralizing antibodies than the Alpha variant. The study was published as a preprint on the bioRxiv website on May 28, 2021 and published in the July 8th, 2021 issue of Nature.

Epidemiological studies demonstrate that the Delta variant is approximately 60% more transmissible than the Alpha variant. The Delta variant's biological characteristics are still relatively unknown. It is characterized by the presence of nine mutations in the Spike protein and has been designated a "Variant of Concern" by several public health organizations including WHO.

In the United Kingdom, for example, the number of cases diagnosed has risen in recent weeks. Between June 23 and 30, 2021, 135,000 people tested positive, with the Delta variant representing 70-90% of sequenced viruses. Two months ago, most cases were imported from India, but a significant rise in the number of indigenous cases has been observed since mid-April.

In France, the Delta variant accounted for over 20% of new cases in the last week of June, compared to 9% the previous week.

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 the Delta variant to antibodies compared with the strains circulating in France and other variants referred to as the British (Alpha) and South African (Beta) 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 SARS-CoV-2 variant Delta from a nasal sample of a patient who developed COVID-19 a few days after returning from India in April 2021. 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 the Delta variant 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 who had received two doses of the Pfizer or AstraZeneca vaccine are still neutralizing but are three to six fold less potent against the Delta variant as compared with the Alpha variant. And the sera of individuals vaccinated with a single dose of the Pfizer or AstraZeneca vaccine are relatively or completely ineffective against the Delta variant."

Olivier Schwartz, co-last author of the study and Head of the Virus and Immunity Unit (Institut Pasteur/CNRS)

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 the Delta variant potentially modify virus binding to the receptor and allow partial escape from the immune response. Ongoing studies are now focused on understanding why this variant is more transmissible.

Source:
Journal reference:

Planas, D., et al. (2021) Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. doi.org/10.1038/s41586-021-03777-9.

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