Background
Solid organ transplant recipients (SOTRs) are highly susceptible to severe COVID-19 due to chronic immunosuppressive treatment aimed at preventing organ rejection, along with associated comorbidities. Their vaccine responses are often diminished compared to the general population. Identifying a biomarker that reflects immune status and predicts vaccination response is crucial for optimizing vaccination strategies. Torque Teno virus (TTV), a component of the human virome, has previously been identified as a marker of immune competence. Our objective was to develop an in-house qPCR assay to measure TTV viral load and evaluate its potential as a predictor of humoral response to SARS-CoV-2 vaccination.
Methods
We designed TTV-specific primers, optimized a Sybr Green qPCR, and created a standard using a topo cloning vector containing TTV isolated from a liver transplant recipient (LTR), which was subsequently sequenced for validation. We determined TTV viral load in plasma samples from LTRs and healthy donors (HD) after administering the initial vaccination regimen (first and second doses) and the booster dose (third dose) of the SARS-CoV-2 vaccine. The humoral response included the measurement of anti-Spike antibodies and neutralizing antibodies.
Results
The prevalence of TTV in LTRs was 91.4% (70/77), compared to 92.9% (13/14) observed in HD. LTRs exhibited a significantly higher TTV viral load after the initial vaccination regimen (median log10(copies/mL): 5.50) compared to HD (median log10(copies/mL): 4.10) (p=0.0001). Among LTRs, those who failed to develop a humoral response had a higher TTV viral load (median log10(copies/mL): 5.94) than those with a successful response (median log10(copies/mL): 4.59) (p<0.0001). This trend persisted after the booster dose, with LTRs showing a median TTV viral load of 5.76 compared to HD at 4.39 (p=0.0027). Non-responders exhibited an even higher TTV viral load (median log10(copies/mL): 5.95) compared to responders (median log10(copies/mL): 5.53) (p=0.004). Notably, there was a correlation between total anti-spike IgG antibody levels in plasma and TTV viral load (p<0.05) in LTRs, both after the initial vaccination regimen and following the booster dose.
Conclusions
In conclusion, a high TTV viral load predicts a poor humoral response to SARS-CoV-2 vaccination. This biomarker should continue to be investigated as a predictor of overall immune status.
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