COVID-19 Omicron Variant Resistant to Monoclonal Antibodies – But Neutralized by Vaccine Booster

3D visualization of mutations in the spike protein of the Omicron variant. Left: Top view. Right: side view. Mutations are indicated in red. They occur throughout the spike protein but particularly in the receptor-binding domain (RBD) and in the region known as the N-terminal domain (NTD). Credit: © Institut Pasteur – Félix Rey

The Omicron variant was first discovered in South Africa in November 2021 and has since spread to many countries. It is expected to become the dominant variant within a few weeks or months. Preliminary epidemiological studies show that the Omicron variant is more transmissible than the currently dominant virus (the delta variant). It is able to spread to individuals who have received two doses of the vaccine and to previously infected individuals. Scientists from the Pasteur Institute and the Vaccine Research Institute, in collaboration with KU Leuven (Leuven, Belgium), Hôpital Européen Georges Pompidou (AP-HP), Inserm and CNRS, have studied the sensitivity of the Omicron variant to monoclonal antibodies used in clinical practice. For the prevention of severe forms of the disease in people at risk, as well as for antibodies in the blood of previously infected individuals SARS-CoV-2 or vaccination. They compared this sensitivity to the sensitivity of the delta variable. Scientists have shown that Omicron is less sensitive than Delta to neutralizing antibodies. The scientists then analyzed the blood of people who had received two doses of either the Pfizer or AstraZeneca vaccines. Five months after vaccination, the antibodies in the blood were no longer able to neutralize the omicron. Loss of efficacy has also been observed in individuals who have been infected with SARS-CoV-2 within the past 12 months. Administration of a booster dose of Pfizer or a single dose of the vaccine in previously infected individuals significantly increased levels of antibodies that were sufficient to neutralize Omicron. Omicron is therefore less sensitive to SARS-CoV-2 antibodies currently used in clinical practice or obtained after two doses of the vaccine.

Preliminary epidemiological studies show that the Omicron variant is more transmissible than the Delta variant. The biological properties of the Omicron variant are still relatively unknown. It contains more than 32 spike protein mutations compared to the first SARS-CoV-2 and was identified as a variant of concern by the World Health Organization on November 26, 2021.

In South Africa, the Omicron variant replaced other viruses within a few weeks and led to a sharp increase in the number of diagnosed cases. Analyzes in different countries indicate that the doubling time for cases is approximately 2 to 4 days. Omicron was discovered in dozens of countries, including France, and became dominant by the end of 2021.

In a new study supported by the European Union Health Emergency Preparedness and Response Authority (HERA), scientists from the Pasteur Institute and the Vaccine Research Institute, in collaboration with KU Leuven (Leuven, Belgium), Orleans Regional Hospital, Hôpital Européen Georges Pompidou (AP-HP) and Inserm, they studied Omicron’s antibody sensitivity compared to the currently dominant Delta variant. The aim of the study was to characterize the efficacy of therapeutic antibodies, as well as antibodies developed previously by individuals infected with SARS-CoV-2 or who have been vaccinated, in neutralizing this novel variant.

Scientists from KU Leuven isolated the Omicron variant of SARS-CoV-2 from a nasal sample of a 32-year-old woman who had developed an Omicron. COVID-19 A few days after his return from Egypt. The isolated virus was immediately sent to scientists at the Pasteur Institute, where therapeutic monoclonal antibodies and serum samples from people vaccinated or previously exposed to SARS-CoV-2 were used to study the sensitivity of the Omicron variant.

The scientists used rapid neutralization assays, developed by the Immunology and Virology Unit at the Pasteur Institute, on an isolated sample of the omicron virus. This collaborative, interdisciplinary effort also included Institut Pasteur virologists specializing in the analysis of viral evolution and protein structure, along with teams from the Regional Hospital Orleans and the Hôpital Européen Georges Pompidou in Paris.

The scientists have begun testing nine monoclonal antibodies in use in clinical practice or currently in preclinical development. Six antibodies lost all antiviral activity, and the other three were 3 to 80 times less effective against Omicron than Delta. The antibodies Bamlanivimab/Etesevimab (a combination developed by Lilly), Casirivimab/Imdevimab (a combination developed by Roche and known as Ronapreve) and Regdanvimab (developed by Celtrion) no longer had any antiviral effect against Omicron. The Tixagevimab/Cilgavimab combination (developed by AstraZeneca under the name Evusheld) was 80 times less effective against Omicron than against Delta.

“We have demonstrated that this highly transmissible variant has acquired significant antibody resistance. Most of the currently available therapeutic monoclonal antibodies against SARS-CoV-2 are inactive,” comments Olivier Schwartz, the study’s latest co-author and head of the Virology and Immunology Unit at the Institute of Pasteur.

The scientists observed that the blood of patients previously infected with COVID-19, which was collected up to 12 months after the onset of symptoms, and the blood of individuals who received two doses of either the Pfizer or AstraZeneca vaccine, five months after vaccination, barely neutralized the Omicron variant. But the serum of individuals who received a booster dose of Pfizer, analyzed one month after vaccination, remained effective against Omicron. However, five to 31 times more antibodies were required to neutralize omicron, compared with delta, in cell culture assays. These findings help shed light on the continued effectiveness of vaccines in protecting against severe forms of the disease.

“Now we need to study the duration of protection for the booster dose. It is possible that vaccines will become less effective in providing protection against infection with the virus, but should continue to protect against severe forms,” ​​explains Olivier Schwartz.

This study shows that the Omicron variant hinders the effectiveness of vaccines and monoclonal antibodies, but also demonstrates the ability of European scientists to work together to identify potential challenges and solutions. While KU Leuven was able to characterize the first case of Omicron infection in Europe using the Belgian genome surveillance system, our collaboration with Institut Pasteur in Paris enabled us to perform this study in record time. There is still much work to be done, but thanks to the support of the European Union’s Health Emergency Preparedness and Response Authority (HERA), it is clear that we are now at a point where scientists from the best centers can work in synergy and progress towards a better understanding of the epidemic and more effective management. To him,” comments Emmanuel Andre, the study’s latest co-author, professor of medicine at KU Leuven (Katholic University of Leuven) and head of the National Reference Laboratory and Genome Surveillance Network for COVID-19 in Belgium.

The scientists concluded that several mutations in the spike protein of the Omicron variant enabled it to largely evade the immune response. Ongoing research is being conducted to determine why this variable is transmitted from one individual to another and to analyze the long-term efficacy of a booster dose.

Reference: “Great escape from SARS-CoV-2 Omicron to neutralizing antibodies” By Delphine Planas, Neil Saunders, Pete Mays, Florence Jevel Benhassen, Cyril Blanchais, Julien Bucheriser, William-Henri Boland, Françoise Borrot, Isabel Staropoli and Frederic Lemoine, Helen Berry, David Vier, Julian Boych, Julian Rodari, Jay Bayla, Simone Delicour, Joren Reimnantes, Sarah Goresin, Caspar Jenin, Bert VanMichelen, Tony Wawena Bucalanga, Joan Marti-Carererasi, Liz Kuipers, Emeric Seuvel Thierry Prazok, Felix Rey, Etienne Simon Laurier, Timothy Bruel, Hugo Moquet, Emmanuel Andre and Olivier Schwartz, December 23, 2021, temper nature.
DOI: 10.1038 / d41586-021-03827-2

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