Effect of SARS-CoV-2 mRNA-Vaccine on the Induction of Myocarditis in Different Murine Animal Models

Figures

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  Figure 1. Effect of 0.2 µg mRNA-vaccine on 5–7 weeks old female (n = 15) and male (n = 13), and on 23-weeks old female (n = 9) and male (n = 11) A/J wt mice. Data is presented as a mean ± SEM. (a) Calculated heart weight to body weight ratio on day 42. Statistical significance was determined by one-way ANOVA: * p = 0.0358, *** p = 0.0007. (b) Evaluation of hsTnT-levels in mouse serum collected on day 42. (c) Histopathological examination of inflammation score in grades in HE stained heart sections on day 42, evaluated by two independent investigators. (d) Echocardiographic examination of ejection fraction using M-mode on day 0 and day 42.

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  Figure 2. Effect of 2.5 µg mRNA-vaccine on 5-weeks old female (n = 11) and male (n = 5) A/J wt mice. Data is presented as a mean ± SEM. (a) Calculated heart weight to body weight ratio on day 42. (b) Determination of hsTnT-values in mouse serum collected on day 42. (c) Histopathological examination of inflammation score in grades in HE stained heart sections on day 42, evaluated by two independent investigators. (d) Determination of produced antibodies against pooled spike protein peptide sequences in mouse serum on day 42 by ELISA.

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  Figure 3. Comparison of 0.2 µg and 2.5 µg mRNA-vaccine on 5-weeks old A/J wt mice with untreated females (n = 4) and males (n = 6). Data is presented as a mean ± SEM. (a) Evaluation of heart weight to body weight ratio on day 42. (b) Comparison of hsTnT-values in mouse serum collected on day 42. (c) Histopathological examination of inflammation score in grades in HE stained heart sections on day 42, evaluated by two independent investigators. (d) Echocardiographic examination of ejection fraction using M-mode on day 0 and day 42.

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  Figure 4. Strain specific differences (BL/6 vs. A/J) of 2.5 µg mRNA-vaccination. Data is presented as a mean ± SEM (vaccine n = 6, untreated n = 5). (a) Comparison of heart weight to body weight ratio on day 42. (b) Measured hsTnT-levels in mouse sera collected on day 42. (c) Histopathological examination of inflammation score in grades in HE stained heart sections on day 42, evaluated by two independent investigators. (d) Echocardiographic assessment of ejection fraction using M-mode on day 0 and day 42.

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  Figure 5. Effect of 2.5 µg mRNA-vaccine on the induction of an experimental autoimmune myocarditis with 150 µg TnI peptide in A/J mice (n = 8). Data is presented as a mean ± SEM. (a) Calculated heart weight to body weight ratio on day 42. (b) Determination of hsTnT-levels in mouse serum collected on day 42. Statistical significance was determined by Mann–Whitney: * p = 0.0373. (c) Histopathological examination of inflammation score in grades in HE stained heart sections on day 42, evaluated by two independent investigators. (d) Echocardiographic assessment of ejection fraction using M-mode on day 0 and day 42 after TnI immunization.

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  Figure 6. Impact of 2.5 µg mRNA-vaccine on BL/6 PD−1+/+ and BL/6 PD-1−/− in combination with immune inhibition. Data is presented as a mean ± SEM (PD−1+/+ untreated n = 5, vaccine n = 6, vaccine + aCTLA-4 n = 6; PD-1−/− untreated n = 5, vaccine female n = 7, male n = 5, vaccine + aCTLA-4 n = 6). (a) Heart weight to body weight ratio on day 42. Statistical significance was determined by t-test, * p = 0.0029. (b) Determination hsTnT-levels of mouse serum collected on day 42. (c) Histopathological examination of inflammation score in grades in HE stained heart sections on day 42, evaluated by two independent investigators. (d) Inflamed heart section of a BL/6 PD-1−/− mouse after vaccination and anti-CTLA-4 co-treatment.