SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice

Author:

Pavan María1,Bok Marina23ORCID,Betanzos San Juan Rafael4ORCID,Malito Juan23,Marcoppido Gisela5,Franco Diego5,Militello Daniela1,Schammas Juan3,Bari Sara1,Stone William6,López Krisangel6,Porier Danielle6,Muller John6,Auguste Albert67ORCID,Yuan Lijuan78ORCID,Wigdorovitz Andrés23,Parreño Viviana238,Ibañez Lorena1ORCID

Affiliation:

1. Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE), Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires ZC 1428, Argentina

2. Incuinta, Instituto Nacional de Tecnología Agropecuaria (INTA), Hurlingham, Buenos Aires ZC 1686, Argentina

3. Instituto de Virología e Innovaciones Tecnológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (IVIT-CONICET), Hurlingham, Buenos Aires ZC 1686, Argentina

4. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Departamento de Química Biológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires ZC 1428, Argentina

5. Centro de Investigaciones en Ciencias Veterinarias y Agronómicas (CICVyA), Instituto Nacional de Tecnología Agropecuaria (INTA), Hurlingham, Buenos Aires ZC 1686, Argentina

6. Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA

7. Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA

8. Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA

Abstract

Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, protection was associated with a significant reduction in virus replication in nasal turbinates and a reduction in virus load in the brain. Employing pseudovirus neutralization assays, we identified Nbs with neutralizing capacity against the Alpha, Beta, Delta, and Omicron variants, including a Nb capable of neutralizing all variants tested. Furthermore, cocktails of different Nbs performed better than individual Nbs at neutralizing two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest the potential of SARS-CoV-2 specific Nbs for intranasal treatment of COVID-19 encephalitis.

Funder

Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación

National Institute of Allergy and Infectious Diseases

Virginia Tech

Publisher

MDPI AG

Reference91 articles.

1. The Global Case Fatality Rate of Coronavirus Disease 2019 by Continents and National Income: A Meta-analysis;Lee;J. Med. Virol.,2022

2. Mathieu, E., Ritchie, H., Rodés-Guirao, L., Appel, C., Gavrilov, D., Giattino, C., Hasell, J., Macdonald, B., Dattani, S., and Beltekian, D. (2023, December 21). Mortality Risk of COVID-19. Available online: https://ourworldindata.org/mortality-risk-covid.

3. World Health Organization (2023, December 12). WHO Coronavirus (COVID-19). Available online: https://covid19.who.int/.

4. (2023, December 21). Ministerio de Salud Argentina Información Epidemiológica. Available online: www.argentina.gob.ar/salud/coronavirus-COVID-19/informacion-epidemiologica/febrero-2023.

5. Coronavirus Infections—More Than Just the Common Cold;Paules;JAMA,2020

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