Abstract
Although recent studies have suggested that the Omicron strain is less severe, the prevalence of long Omicron variants and their subvariant waves continues today. Here, we analyze the pathological characteristics of SARS-CoV-2 variants in cynomolgus macaques. Prolonged re-challenge analysis results in the establishment of re-infection in some macaques with both the same strain and different strains. Omicron infection shows low pathogenicity; however, all macaques that developed pneumonia were inoculated with Omicron strains at the second inoculation. Interestingly, antibodies against the Wuhan, Alpha, and Delta strains are strongly induced regardless of the strain, but antibodies against Omicron strains are not. Moreover, despite the re-infection strain, antibody levels against the Wuhan strain are highest, suggesting original antigenic sin. In addition, Omicron infection induces weaker antigen-specific T-cell responses. These results indicate that immune responses to viral infection differ between the variants, and these differences could inform vaccine development strategies.
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Acknowledgments
We thank the members and veterinary staff of HAMRI Co., Ltd. and the Corporation for Production and Research of Laboratory Primates for their technical expertise and assistance with animal care and sample processing using cynomolgus macaques. This work was supported by the Japan Agency for Medical Research and Development (AMED), Research Program on Emerging and Re-emerging Infectious Diseases under JP20fk0108414 (to E.U., T.O., Y.Y.), JP21fk0108582 (to E.U.), by the AMED Strategic Center of Biomedical Advanced Vaccine Research and Development for Preparedness and Response (SCARDA), Japan Initiative for World-leading Vaccine Research and Development Centers under JP223fa627007 (to E.U., T.O., Y.Y.), JP223fa727002 (to Y.Y.), JP223fa627005 (to Y.Y.), by the Japan Society for the Promotion of Science (JSPS), KAKENHI Grant-in-Aid for Exploratory Research under 21K19395 (to E.U. and Y.Y.), by the Japan Science and Technology Agency (JST), under JPMJPF2017 (to Y.Y.). We would like to thank S.E.S. Translation and Proofreading Services and Editage (www.editage.jp) for English language editing.
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E.U. and Y.Y. designed the experiments. E.U., M.H., M.F., and K.U. performed the virological and the biological assays. T.O. analyzed CT images and veterinary pathology. S.N. and H.K. performed gene cloning and protein purification. E.U. and Y.Y. wrote the paper, and all authors reviewed the manuscript.
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Urano, E., Okamura, T., Higuchi, M. et al. Pathological characteristics of SARS-CoV-2 variants and immune responses induced in a COVID-19 macaque model. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09684-x
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DOI: https://doi.org/10.1038/s42003-026-09684-x
