- All experiments were conducted in six- to eight-week old mice.

University of Michigan - Ann Arbor

- Tissue and Culture Methods
- Vaccines used for Comparison
- Animal Models
- Study Design
- Lung Abnormality Grading System

Methods used in Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

Tseng C, Sbrana E, Iwata-Yoshikawa N et al. Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus. PLoS ONE. 2012;7(4):e35421. doi:10.1371/journal.pone.0035421

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035421

Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

- Vero E6 tissue cultures were grown using Dulbecco’s modified minimum essential medium. 
- The SARS-CoV strain was provided by the Centers for Disease Control and Prevention


Tissue and Culture Methods used in Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

- Four different types of vaccines were used for comparisons in this study.
       - Two whole virus vaccines were evaluated 
             - One double-inactivated vaccine (DIV)
             - One inactivated vaccine packaged with alum adjuvant (BPV)
       - Recombinant DNA spike (S) protein vaccine (SV)
       - Virus-like particle vaccine containing SARS-CoV spike (S) protein, the 
          nucleocapsid (N), envelope (E) and membrane (M).


Vaccines used for Comparison in Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

- Experimental Groups 
      - Adjuvanted (alum) and non-adjuvanted (PBS) vaccines at various doses 
         were administered to mice intramuscularly on days 0 and 28.
      - Each experimental group consisted of 12-13 mice.
      - 5 from each group were sacrificed on Day 56 in order to assess serum 
         neutralizing antibody titers and lung histopathology. The remaining 
         mice were challenged with SARS-CoV. 
      - Challenged mice were sacrificed on Day 58.  
- Control Group
      - Mice that received PBS, alum, trivalent inactivated influenza vaccine or 
         live SARS-CoV were considered controls



Study Design used in Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

- Histopathology was graded on a 0-4 scale
      - 0-2 indicates degree of cellular infiltration 
      - 3-4 indicates the degree of epithelial cell necrosis 


Lung Abnormality Grading System used in Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

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