Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients.

Antiviral prophylaxis has proved successful for prevention of cytomegalovirus (CMV) disease in solid organ transplant (SOT) patients; though emerging data suggest that antiviral agents interfere with immunity, and may inhibit immune priming. In this context, we investigated levels and phenotype of primary CMV-specific immune responses that developed during antiviral prophylaxis in a cohort of CMV seronegative recipients (R(-) ) of a SOT from a seropositive donor (D(+) ). We longitudinally monitored CMV viral load, antibodies and levels of the negative immuno-modulator IL-10. PBMC were stimulated with CMV-specific peptide libraries to measure CD137 activation marker on CMV-specific T-cells and levels of PD-1 receptor, which is over expressed on exhausted T-cells. Unexpectedly, the majority (13/18) of D(+) R(-) patients who developed a primary CMV response showed early post-transplant CMV-specific responses, though levels of PD-1 on CMV-specific T-cells remained elevated throughout prophylaxis. A strong inverse association was found between levels of plasma IL-10 and CMV-specific cellular immune responses. Our study suggests that during prophylaxis, subclinical CMV infection might have occurred in the D(+) R(-) patients, and primary CMV-specific responses were detected early post-transplant when levels of plasma IL-10 were low. Extended prophylaxis or antiviral treatment did not appear to suppress CMV-specific antibodies or T-cells, which, however, showed exhaustion phenotypes.