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Generation and Effect Testing of a SARS-CoV-2 RBD-Targeted Polyclonal Therapeutic Antibody Based on a 2-D Airway
Yunjiao He1, Jing Qu2, Lan Wei2,3
1School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Abstract:
Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US FDA has approved several therapeutics and vaccines worldwide through the emergency use authorization in response to the rapid spread of COVID-19. Nevertheless, the efficacies of these treatments are being challenged by viral escape mutations. There is an urgent need to develop effective treatments protecting against SARS-CoV-2 infection and to establish a stable effect-screening model to test potential drugs. Polyclonal antibodies (pAbs) have an intrinsic advantage in such developments because they can target rapidly mutating viral strains as a result of the complexity of their binding epitopes. In this study, we generated anti-receptor-binding domain (anti-RBD) pAbs from rabbit serum and tested their safety and efficacy in response to SARS-CoV-2 infection both in vivo and ex vivo. Primary human bronchial epithelial two-dimensional (2-D) organoids were cultured and differentiated to a mature morphology and subsequently employed for SARS-CoV-2 infection and drug screening. The pAbs protected the airway organoids from viral infection and tissue damage. Potential side effects were tested in mouse models for both inhalation and vein injection. The pAbs displayed effective viral neutralization effects without significant side effects. Thus, the use of animal immune serum-derived pAbs might be a potential therapy for protection against SARS-CoV-2 infection, with the strategy developed to produce these pAbs providing new insight into the treatment of respiratory tract infections, especially for infections with viruses undergoing rapid mutation.
Insights
Rabbit-derived polyclonal antibodies targeting the SARS-CoV-2 receptor-binding domain show safety and efficacy. These antibodies protected airway organoids from infection and demonstrated neutralization effects in vivo without significant side effects.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, necessitates new treatments due to viral mutations challenging existing therapies.
- Polyclonal antibodies (pAbs) offer a potential advantage against rapidly mutating viruses due to their multiple binding epitopes.
Purpose of the Study:
- To develop and evaluate the safety and efficacy of anti-receptor-binding domain (anti-RBD) polyclonal antibodies derived from rabbit serum against SARS-CoV-2.
- To establish and utilize a 2-D human bronchial epithelial organoid model for drug screening against SARS-CoV-2.
Main Methods:
- Generated anti-RBD polyclonal antibodies from rabbit serum.
- Utilized 2-D human bronchial epithelial organoids for SARS-CoV-2 infection and drug screening.
- Assessed antibody safety and efficacy in vivo using mouse models (inhalation and intravenous injection).
Main Results:
- The generated polyclonal antibodies effectively protected airway organoids from SARS-CoV-2 infection and subsequent tissue damage.
- In vivo studies in mice demonstrated significant viral neutralization effects without notable adverse side effects.
- The 2-D organoid model proved effective for screening potential SARS-CoV-2 therapeutics.
Conclusions:
- Animal immune serum-derived polyclonal antibodies represent a promising therapeutic strategy for combating SARS-CoV-2 infection.
- The developed antibody production strategy offers insights into treating respiratory tract infections, particularly those caused by rapidly mutating viruses.
