Out of 102 monoclonal antibodies tested, only Cv2.1169 and Cv2.3194 cross-neutralized all variants of concern, including Omicron BA.1 and BA.2 subvariants.
Monoclonal antibodies were once considered the gold standard of COVID-19 treatment. However, the emergence of the highly infectious Omicron variant rendered them largely ineffective. The US Food and Drug Administration (FDA) even paused distribution of many monoclonal antibodies after Omicron became the dominant variant.
One large-scale study of monoclonal antibodies, published in the Journal of Experimental Medicine, sought to determine if any were effective against COVID-19 variants of concern, including Omicron. The research was led by the Institut Pasteur, Université Paris Cité, and the Institut national de la santé et de la recherche médicale (INSERM).
“The broadly neutralizing antibodies we described were more efficient in vitro than many anti–SARS-CoV-2 monoclonals previously approved by the FDA for treatment or prevention,” said Hugo Mouquet, the head of the Laboratory of Humoral Immunology at the Institut Pasteur and a lead investigator of the study. “Therefore, we are pretty confident that they represent premium candidates for pre-exposure prophylaxis in immunocompromised patients.”
Long-term protection against severe COVID-19 is generated by memory B-cell and antibody responses to the virus’s spike protein. The investigators conducted a detailed characterization of 102 SARS-CoV-2 spike monoclonal antibodies, cloned from the memory B-cells of 10 COVID-19 convalescents.
Among all the monoclonal antibodies tested, only Cv2.1169 and Cv2.3194 cross-neutralized all variants of concern, including Omicron BA.1 and BA.2 subvariants. These were the most potent RBD-targeting antibodies.
“One aspect of our work highlights the role of IgA antibodies for a broad SARS-CoV-2 neutralization,” Mouquet said. “When studying immune responses against pathogens affecting mucosal tissues, we thus consider that IgA-mediated antibody response should be systematically investigated, including in the quest of isolating broadly neutralizing monoclonal antibodies.”
Cv2.1169 was isolated from a mucosa-derived, immunoglobin A, memory B cell, demonstrating potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animals. Cv2.1169 is a type of antibody produced by B cells in the body’s mucosal tissues, including the respiratory tract, and may be crucial in ensuring early response to respiratory pathogens.
These monoclonal antibodies may be especially beneficial in immunocompromised persons. “A key point is that those monoclonals have been engineered for extending their half-lives and therefore have an expected prolonged effect in people but would still require regular injections, possibly every few months, to maintain protective antibody titers,” said Mouquet. This extended half-life would bolster immunity for people who did not generate an adequate immune response to COVID-19 vaccination.