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A Broad and Potent H1-Specific Human Monoclonal Antibody Produced in Plants Prevents Influenza Virus Infection and Transmission in Guinea Pigs

1
Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
2
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham 845 19th Street South, Birmingham, AL 35294, USA
3
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), 28130 Madrid, Spain
4
PlantForm Corporation, 1920 Yonge St., Suite 200, Toronto, ON M4S 3E2, Canada
5
AntoXa Corporation, 1920 Yonge St., Suite 200, Toronto, ON M4S 3E2, Canada
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2020, 12(2), 167; https://doi.org/10.3390/v12020167
Received: 9 January 2020 / Revised: 25 January 2020 / Accepted: 30 January 2020 / Published: 2 February 2020
(This article belongs to the Section Animal Viruses)
Although seasonal influenza vaccines block most predominant influenza types and subtypes, humans still remain vulnerable to waves of seasonal and new potential pandemic influenza viruses for which no immunity may exist because of viral antigenic drift and/or shift. Previously, we described a human monoclonal antibody (hMAb), KPF1, which was produced in human embryonic kidney 293T cells (KPF1-HEK) with broad and potent neutralizing activity against H1N1 influenza A viruses (IAV) in vitro, and prophylactic and therapeutic activities in vivo. In this study, we produced hMAb KPF1 in tobacco plants (KPF1-Antx) and demonstrated how the plant-produced KPF1-Antx hMAb possesses similar biological activity compared with the mammalian-produced KPF1-HEK hMAb. KPF1-Antx hMAb showed broad binding to recombinant HA proteins and H1N1 IAV, including A/California/04/2009 (pH1N1) in vitro, which was comparable to that observed with KPF1-HEK hMAb. Importantly, prophylactic administration of KPF1-Antx hMAb to guinea pigs prevented pH1N1 infection and transmission in both prophylactic and therapeutic experiments, substantiating its clinical potential to prevent and treat H1N1 infections. Collectively, this study demonstrated, for the first time, a plant-produced influenza hMAb with in vitro and in vivo activity against influenza virus. Because of the many advantages of plant-produced hMAbs, such as rapid batch production, low cost, and the absence of mammalian cell products, they represent an alternative strategy for the production of immunotherapeutics for the treatment of influenza viral infections, including emerging seasonal and/or pandemic strains. View Full-Text
Keywords: orthomyxovirus; influenza virus; antivirals; plantibody; prophylactic; therapeutic; monoclonal antibody; antibody treatment; neutralizing antibody; virus infection; virus transmission orthomyxovirus; influenza virus; antivirals; plantibody; prophylactic; therapeutic; monoclonal antibody; antibody treatment; neutralizing antibody; virus infection; virus transmission
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Park, J.-G.; Ye, C.; Piepenbrink, M.S.; Nogales, A.; Wang, H.; Shuen, M.; Meyers, A.J.; Martinez-Sobrido, L.; Kobie, J.J. A Broad and Potent H1-Specific Human Monoclonal Antibody Produced in Plants Prevents Influenza Virus Infection and Transmission in Guinea Pigs. Viruses 2020, 12, 167.

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