Identification of broadly neutralizing SARS-CoV-2 monoclonal antibodies

Institut Pasteur | 06-17-2022
Identification of broadly neutralizing SARS-CoV-2 monoclonal antibodies
Structure of the variable domains of the Cv2.1169 antibody (purple) in complex with the S protein domain involved in SARS-CoV-2 receptor binding (receptor binding domain or RBD in yellow), obtained by X-ray crystallography in the Structural Virology laboratory (Institut Pasteur). Credit: © Hugo Mouquet, Institut Pasteur

Although the different SARS-CoV-2 variants currently in circulation are undoubtedly less severe in vaccinated individuals in the general population, immunocompromised people are at greater risk of developing severe forms of COVID-19. Monoclonal antibodies currently offer the best approach, both as a preventive and curative treatment for these patients. Scientists from the Institut Pasteur and Inserm identified two potent neutralizing antibodies from convalescent COVID-19 individuals that proved effective against SARS-CoV-2 variants of concern. These human antibodies are prime candidates for the development of immunotherapies to prevent severe forms and/or treat COVID-19. The findings were published in The Journal of Experimental Medicine on June 15, 2022.

Antibody and memory B cell responses to SARS-CoV-2 spike (S) proteins contribute to long-term immune protection against severe forms of COVID-19. Immunotherapy based on neutralizing antibodies can also prevent severe forms in individuals who fail to respond to vaccination, such as immunocompromised patients, who number approximately 230,000 people in France. The clinical benefits of anti-SARS-CoV-2 “monoclonal” antibodies have already been established in clinical trials to treat COVID-19 patients and prevent the onset of severe forms.

In this study conducted by scientists in the Institut Pasteur’s Humoral Immunology laboratory led by Dr. Hugo Mouquet (a joint Inserm unit), in collaboration with several Institut Pasteur and Inserm teams, the immune response to SARS-CoV-2 in convalescent COVID-19 individuals was investigated through detailed analysis of antibodies targeting the SARS-CoV-2 S protein at serological level (antibodies in the bloodstream), cellular level (antibody-producing B cells) and molecular level (monoclonal antibodies). In particular, detailed characterization of a hundred human monoclonal antibodies specific to the SARS-CoV-2 S protein, cloned from memory B cells isolated from convalescents, revealed the diversity of their antiviral functions, such as the neutralization or destruction of infected cells.

“Two of the potent neutralizing antibodies identified, Cv2.1169 and Cv2.3194, are broad-spectrum antibodies meaning that they are effective against SARS-CoV-2 variants of concern: Alpha, Beta, Gamma, Delta and Omicron BA.1 and BA.2. The monoclonal antibody Cv2.1169, tested in animal models of SARS-CoV-2 infection, demonstrated prophylactic (preventive) and therapeutic activity in vivo,” commented Hugo Mouquet, Head of the Institut Pasteur’s Humoral Immunology laboratory (a joint Inserm unit).

Since the Cv2.1169 antibody was isolated from a mucosa-derived B cell, this type of antibodies in the mucosa of convalescent individuals could help protect them from infection with SARS-CoV-2 variants.

“These potent human broadly neutralizing monoclonal antibodies are promising candidates for the development of immunotherapies in humans to prevent and/or treat COVID-19,” added Hugo Mouquet.

The Institut Pasteur has filed an international patent application to protect the neutralizing antibodies identified in this study [“Human neutralizing monoclonal antibodies against SARS-CoV-2 and their use thereof” (PCT/EP2022/058777)]. This patent application is the subject of an exclusive worldwide license agreement with SpikImm – a biotech established by Truffle Capital and the Institut Pasteur – which develops the antibodies as easy-to-administer (by intramuscular injection), long-acting antibodies for preventing COVID-19 (pre-exposure prophylaxis) in immunocompromised patients who often exhibit a weak or no immune response after full vaccination. SpikImm plans to start clinical trials in July 2022. The French National Ad Hoc Steering Committee for Therapeutic Trials and Other Research (CAPNET) recently awarded this Phase I trial the “National Research Priority” label.


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