Neutralizing antibody-dependent and -independent immune responses against SARS-CoV-2 in cynomolgus macaques

• Published in: Virology (New York, N.Y.) Vol. 554; pp. 97 - 105
• Main Authors: Ishigaki, Hirohito, Nakayama, Misako, Kitagawa, Yoshinori, Nguyen, Cong Thanh, Hayashi, Kaori, Shiohara, Masanori, Gotoh, Bin, Itoh, Yasushi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2021
• Subjects: animal models; Animals; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; antiviral agents; body temperature; cell-mediated immunity; Coronavirus infections; COVID-19 - immunology; COVID-19 - pathology; COVID-19 - virology; Cytokines - blood; Disease Models, Animal; Female; humans; immune response; Infectious Disease; Interferon-gamma - immunology; interferons; Macaca fascicularis; Male; Mouth - virology; Nasal Cavity - virology; neutralization; neutralizing antibodies; Neutralizing antibody; Nonhuman primate; pathogenicity; patients; Pneumonia; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; radiography; SARS-CoV-2; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; SARS-CoV-2 - physiology; signs and symptoms (animals and humans); T-lymphocytes; T-Lymphocytes - immunology; Th1 response; Thrombus; vaccine development; vaccines; Viral Load; viral pneumonia; virology; X-radiation; SARS-CoV-2; Pneumonia; Th1 response; Nonhuman primate; Thrombus; Neutralizing antibody
• ISSN: 0042-6822; 1096-0341; 1096-0341
• DOI: 10.1016/j.virol.2020.12.013

We examined the pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in cynomolgus macaques for 28 days to establish an animal model of COVID-19 for the development of vaccines and antiviral drugs. Cynomolgus macaques infected with SARS-CoV-2 showed body temperature rises and X-ray radiographic pneumonia without life-threatening clinical signs of disease. A neutralizing antibody against SARS-CoV-2 and T-lymphocytes producing interferon (IFN)-γ specifically for SARS-CoV-2 N-protein were detected on day 14 in one of three macaques with viral pneumonia. In the other two macaques, in which a neutralizing antibody was not detected, T-lymphocytes producing IFN-γ specifically for SARS-CoV-2 N protein increased on day 7 to day 14, suggesting that not only a neutralizing antibody but also cellular immunity has a role in the elimination of SARS-CoV-2. Thus, because of similar symptoms to approximately 80% of patients, cynomolgus macaques are appropriate to extrapolate the efficacy of vaccines and antiviral drugs for humans. •Cynomolgus macaques infected with SARS-CoV-2 showed fever.•SARS-CoV-2 caused X-ray radiographic and histological pneumonia in cynomolgus macaques.•A thrombus was found in cynomolgus macaques infected with SARS-CoV-2.•A neutralizing antibody against SARS-CoV-2 were detected in one of three macaques.•T-lymphocytes producing IFN-γ specifically for SARS-CoV-2 increased in infected macaques.