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Author Spotlight: A Pseudotype Virus System for Assessing Omicron Subvariants and Neutralizing Antibodies in SARS-CoV-2 Research
Published on: September 8, 2023
Pathological characteristics of SARS-CoV-2 variants and immune responses induced in a COVID-19 macaque model
Emiko Urano1, Tomotaka Okamura1, Mahoko Higuchi1
1Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki, Japan.
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.
Insights
SARS-CoV-2 Omicron variants cause re-infection and pneumonia in macaques, despite initial low pathogenicity. Immune responses vary, impacting vaccine strategies against evolving strains.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- The Omicron variant of SARS-CoV-2, despite being considered less severe, continues to circulate globally.
- Understanding the pathological characteristics and immune responses to different SARS-CoV-2 variants is crucial for public health.
- Re-infection with SARS-CoV-2 variants poses a significant challenge in managing the pandemic.
Purpose of the Study:
- To analyze the pathological characteristics of SARS-CoV-2 variants, including Omicron, in a non-human primate model (cynomolgus macaques).
- To investigate the immune responses, including antibody production and T-cell activity, following re-infection with different SARS-CoV-2 strains.
- To evaluate the implications of observed immune responses for the development of effective vaccines against SARS-CoV-2 variants.
Main Methods:
- Cynomolgus macaques were subjected to prolonged re-challenge analysis with various SARS-CoV-2 strains (Wuhan, Alpha, Delta, Omicron).
- Pathological characteristics, including the development of pneumonia, were assessed after primary and secondary inoculations.
- Humoral (antibody levels) and cellular (T-cell responses) immune responses were measured against different viral strains.
Main Results:
- Omicron infection demonstrated low initial pathogenicity, but macaques inoculated with Omicron strains during the second inoculation developed pneumonia.
- Antibodies against Wuhan, Alpha, and Delta strains were induced irrespective of the infecting strain, while Omicron-specific antibodies were poorly induced.
- Antibody levels against the original Wuhan strain remained highest even after re-infection with different variants, suggesting original antigenic sin.
- Omicron infection resulted in weaker antigen-specific T-cell responses compared to other variants.
Conclusions:
- Immune responses to SARS-CoV-2 infection differ significantly across variants, particularly with Omicron.
- The phenomenon of original antigenic sin may influence protective immunity against subsequent infections.
- Understanding these variant-specific immune dynamics is essential for designing updated and effective SARS-CoV-2 vaccines.
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