Harold Marcotte

Most approved antibodies against SARS-CoV-2 are ineffective against Omicron subvariants, highlighting the urgent need for alternative therapies. Secretory IgA (sIgA) is the predominant immunoglobulin type in secretions and plays a crucial role in mucosal defenses. Results from our previous VR project, "Mucosal Immunity Against SARS-CoV-2 - A Neglected Field", suggested that both dimeric and sIgA1 antibodies were superior to IgG in neutralizing SARS-CoV-2, providing protection in a mouse model through intranasal delivery. In this project, we plan to further advance the development of a broadly neutralizing IgA antibody lead candidate by generating a stable cell line with the antibody genes integrated into the genome and optimizing the production and purification processes under standard laboratory conditions. All relevant data and protocols used during cell line development and characterization will ensure compliance with regulatory standards and facilitate transfer to GMP facilities. This proof of principal proposal will help us to achieve the next goal, i.e., to further develop and commercialize the lead IgA antibody candidates as a nasal spray to block viral entry and enhance mucosal immunity against future SARS-CoV-2 variants. If successful, this approach could be extended to develop a cocktail of broadly neutralizing IgA antibodies against SARS-CoV-2 for use in a nasal spray. This will help us achieve our long-term goal of preparing for the next pandemic.