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

COVID Omicron Variant Spike Protein
COVID Omicron Variant Spike Protein

3D visualization of mutations in the spike protein of the Omicron variant. Left: overhead view. Right: lateral view. Mutations are indicated in red. They occur all over 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 detected for the first time 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. Initial epidemiological studies show that the Omicron variant is more transmissible than the currently dominant virus (the Delta variant). It is capable of spreading to individuals who have received two vaccine doses and to previously infected individuals. Scientists from the Institut Pasteur and the Vaccine Research Institute, in collaboration with KU Leuven (Leuven, Belgium), Orléans Regional Hospital, Hôpital Européen Georges Pompidou (AP-HP), Inserm and the CNRS, studied the sensitivity of the Omicron variant to monoclonal antibodies used in clinical practice to prevent severe forms of the disease in people at risk, as well as to antibodies in the blood of individuals previously infected with

The scientists used rapid neutralization assays, developed by the Institut Pasteur’s Virus and Immunity Unit, on the isolated sample of the Omicron virus. This collaborative multidisciplinary effort also involved the Institut Pasteur’s virologists and specialists in the analysis of viral evolution and protein structure, together with teams from Orléans Regional Hospital and Hôpital Européen Georges Pompidou in Paris.

The scientists began by testing nine monoclonal antibodies used 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 against 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 demonstrated that this highly transmissible variant has acquired significant resistance to antibodies. Most of the therapeutic monoclonal antibodies currently available against SARS-CoV-2 are inactive,” comments Olivier Schwartz, co-last author of the study and Head of the Virus and Immunity Unit at the Institut Pasteur.

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

“We now need to study the length of protection of the booster dose. The vaccines probably become less effective in offering protection against contracting the virus, but they should continue to protect against severe forms,” explains Olivier Schwartz.

“This study shows that the Omicron variant hampers the effectiveness of vaccines and monoclonal antibodies, but it also demonstrates the ability of European scientists to work together to identify challenges and potential solutions. While KU Leuven was able to describe the first case of Omicron infection in Europe using the Belgian genome surveillance system, our collaboration with the Institut Pasteur in Paris enabled us to carry out this study in record time. There is still a great deal of work to do, but thanks to the support of the European Union’s Health Emergency Preparedness and Response Authority (HERA), we have clearly now reached a point where scientists from the best centers can work in synergy and move towards a better understanding and more effective management of the pandemic,” comments Emmanuel André, co-last author of the study, a Professor of Medicine at KU Leuven (Katholieke Universiteit Leuven) and Head of the National Reference Laboratory and the genome surveillance network for COVID-19 in Belgium.

The scientists concluded that the many 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 variant is more transmissible from one individual to the next and to analyze the long-term effectiveness of a booster dose.

Reference: “Considerable escape of SARS-CoV-2 Omicron to antibody neutralization” by Delphine Planas, Nell Saunders, Piet Maes, Florence Guivel-Benhassine, Cyril Planchais, Julian Buchrieser, William-Henry Bolland, Françoise Porrot, Isabelle Staropoli, Frederic Lemoine, Hélène Péré, David Veyer, Julien Puech, Julien Rodary, Guy Baela, Simon Dellicour, Joren Raymenants, Sarah Gorissen, Caspar Geenen, Bert Vanmechelen, Tony Wawina-Bokalanga, Joan Martí-Carrerasi, Lize Cuypers, Aymeric Sève, Laurent Hocqueloux, Thierry Prazuck, Félix Rey, Etienne Simon-Lorrière, Timothée Bruel, Hugo Mouquet, Emmanuel André and Olivier Schwartz, 23 December 2021, Nature.
DOI: 10.1038/d41586-021-03827-2

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