Pathological characteristics of SARS-CoV-2 variants and immune responses induced in a COVID-19 macaque model

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.