IgA for mucosal prophylaxis and treatment of COVID-19

SARS-CoV-2 is a novel coronavirus responsible for the current COVID-19 pandemic which causes mild or even asymptomatic respiratory infections in most people, but the elderly and those with underlying health issues are particularly at risk of a more severe clinical course. The extraordinary scientific response to the crisis has brought forth a plethora of therapeutic strategies in particular vaccines, which, however, do not generally help the infected or those with dysfunctional immune systems. Other well-established strategies such as passive immunotherapy using intravenously applied virus neutralizing antibodies can provide immediate protection and are suitable for the immunosuppressed, but do not attack the virus at the front line of the disease. Also, they might be unsuitable for prophylaxis and their efficacy may be limited or delayed. Agents applied directly to the primary mucosal sites of infection in the nasal cavity and the lung through nasal drops or inhalation could stop the virus during the early stages, resulting in a quicker and more favourable clinical outcome even in patients with underlying conditions. Currently most of the therapeutic antibodies on the market are of the IgG type, which is the major antibody class in human serum. However, Immunoglobulin A (IgA), which is the predominant antibody class in the external secretions of mucosal surfaces where it serves as a first line of defence by neutralizing invading pathogens, is increasingly gaining attention as a biopharmaceutical for the treatment of infectious diseases. We aim to engineer IgA antibodies that specifically target SARS-CoV-2 and administration to the nasal cavity or lungs could provide a new approach for the treatment of COVID-19, reduce viral carriage, and prevent transmission. Still, the required quantities for population wide treatment would completely swamp existing manufacturing capacity and would call for unprecedented investments in fixed-volume fermenters. The demand, however, could be met by large-scale production in plants, an approach known as molecular pharming. We will generate anti-SARS-CoV-2 IgA antibodies in the tobacco-related Nicotiana benthamiana plants, which is a well-established platform that has already been used to produce the ZMapp antibody cocktail during the 2014 West Africa Ebola outbreak and 50 million doses of a vaccine against seasonal flu in an unprecedented timescale. This passive immunotherapy approach using plant-produced mucosal antibodies that neutralise SARS-CoV-2 at primary sites of infection could be a strategy for prevention of transmission and treatment of COVID-19 in a critical-care environment, as well as providing prophylaxis for at-risk populations while also addressing issues of scalability, affordability, and accessibility on a global scale.

SARS-CoV-2 is a novel coronavirus responsible for the current COVID-19 pandemic which causes mild or even asymptomatic respiratory infections in most people, but the elderly and those with underlying health issues are particularly at risk of a more severe clinical course. The extraordinary scientific response to the crisis has brought forth a plethora of therapeutic strategies in particular vaccines, which, however, do not generally help the infected or those with dysfunctional immune systems. Other well-established strategies such as passive immunotherapy using intravenously applied virus neutralizing antibodies can provide immediate protection and are suitable for the immunosuppressed, but do not attack the virus at the front line of the disease. Also, they might be unsuitable for prophylaxis and their efficacy may be limited or delayed. Agents applied directly to the primary mucosal sites of infection in the nasal cavity and the lung through nasal drops or inhalation could stop the virus during the early stages, resulting in a quicker and more favourable clinical outcome even in patients with underlying conditions. Currently most of the therapeutic antibodies on the market are of the IgG type, which is the major antibody class in human serum. However, Immunoglobulin A (IgA), which is the predominant antibody class in the external secretions of mucosal surfaces where it serves as a first line of defence by neutralizing invading pathogens, is increasingly gaining attention as a biopharmaceutical for the treatment of infectious diseases. We aim to engineer IgA antibodies that specifically target SARS-CoV-2 and administration to the nasal cavity or lungs could provide a new approach for the treatment of COVID-19, reduce viral carriage, and prevent transmission. Still, the required quantities for population wide treatment would completely swamp existing manufacturing capacity and would call for unprecedented investments in fixed-volume fermenters. The demand, however, could be met by large-scale production in plants, an approach known as 'molecular pharming'. We will generate anti-SARS-CoV-2 IgA antibodies in the tobacco-related Nicotiana benthamiana plants, which is a well-established platform that has already been used to produce the ZMapp antibody cocktail during the 2014 West Africa Ebola outbreak and 50 million doses of a vaccine against seasonal flu in an unprecedented timescale. This passive immunotherapy approach using plant-produced mucosal antibodies that neutralise SARS-CoV-2 at primary sites of infection could be a strategy for prevention of transmission and treatment of COVID-19 in a critical-care environment, as well as providing prophylaxis for at-risk populations while also addressing issues of scalability, affordability, and accessibility on a global scale.