Coronavirus particles, illustration - SARS-CoV-2 virus
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Two potent neutralizing antibodies from convalescent COVID-19 individuals have been found that are effective against SARS-CoV-2 variants of concern. These human antibodies, identified by scientists from the Institut Pasteur and Inserm, are prime targets for development of immunotherapies to prevent severe forms and to treat the infection.

The report was published in The Journal of Experimental Medicine last week.

Although the different SARS-CoV-2 variants currently in circulation are less severe in most people, the immunocompromised are still at greater risk. Monoclonal antibodies currently offer the best approach, both as a preventive and curative treatment for these patients

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.  Last year, a team that included researchers from Institut Pasteur, showed that SARS-CoV-2 infection induces polyfunctional antibodies that can activate natural killer cells or the complement system to attack infected cells. While the antibody levels are slightly lower in asymptomatic individuals, the polyfunctional antibodies were found in all infected people.

Immunotherapy based on neutralizing antibodies can prevent severe forms in individuals who fail to respond to vaccination, such as immunocompromised patients. The authors note that 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 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,” said Mouquet.

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 Mouquet.

The Institut Pasteur has filed an international patent application to protect the neutralizing antibodies identified in this study. 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 delivered by intramuscular injection for preventing COVID-19 (pre-exposure prophylaxis) in immunocompromised patients. SpikImm plans to start clinical trials in July 2022.

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