Criteria to define interruption of transmission of human cytomegalovirus from organ donor to recipient

Abstract

SummaryIn this review article, we consider results suggesting that transmission of human cytomegalovirus (HCMV) from a donor of a solid organ to an immunologically naive individual can be reduced. Two randomized controlled trials have been conducted recently, one of active immunization of recipients pretransplant and another of passive immunization with monoclonal antibodies specific for HCMV given at the time of transplant. Although the available data are encouraging-providing evidence of a reduction in the incidence of HCMV viraemia-they fall short of what would be required to prove definitively that transmission has been completely prevented. Here, we reflect on these studies and propose a set of 5 criteria, which, if satisfied in the future, could be taken as proof that active and/or passive immunization against HCMV effectively interrupts transmission of virus from the donor. We suggest that these criteria are considered when designing future randomized controlled trials.

Original Antigenic Sin Shapes the Immunological Repertoire Evoked by Human Cytomegalovirus Glycoprotein B/MF59 Vaccine in Seropositive Recipients

“…Human Cytomegalovirus (HCMV) infection is common, with seroprevalence ranging from 60 to 100% (1). HCMV can promote substantial mortality and morbidity in immunocompromised individuals, including solid organ transplant (SOT) recipients (2). In these patients, CMV end-organ disease results from primary infection, reinfection or reactivation (3).…”

New vaccines and antiviral drugs for cytomegalovirus

“…Compared to recipients of placebo, the vaccine did not reduce the incidence of infection or end-organ disease, but did reduce the severity of disease. Measures of viral load were not available in those days but, because natural history studies show a strong correlation between a high viral load and the development of end-organ disease, it is very likely that this vaccine had its beneficial clinical effects by reducing viral loads post-transplant (3,4,18). In 2011, our group reported that administration of a vaccine based on theCMV glycoprotein B plus MF59 adjuvant reduced parameters of viral load and the correlate of protection was the titre of antibodies made against glycoprotein B.…”

An explanation for posttransplant late‐onset disease associated with CMV prophylaxis

“…It will be important to determine if prophylaxis with drugs other than valganciclovir, eg, letermovir, have the same effect after solid organ transplant. They also provide valuable information on which immune responses may be protective against CMV posttransplant, thereby providing a target for novel vaccines to aim for if we wish them to protect transplant patients . Finally, they draw attention to the fact that the risk borne by CMV seronegative recipients can be reduced if they mount an effective immune response against this virus and should encourage the conduct of more randomised controlled trials to give prototype CMV vaccines pretransplant as a way of controlling CMV viral load post‐transplant .…”

“…They also provide valuable information on which immune responses may be protective against CMV posttransplant, thereby providing a target for novel vaccines to aim for if we wish them to protect transplant patients . Finally, they draw attention to the fact that the risk borne by CMV seronegative recipients can be reduced if they mount an effective immune response against this virus and should encourage the conduct of more randomised controlled trials to give prototype CMV vaccines pretransplant as a way of controlling CMV viral load post‐transplant . A new phase 2 randomised controlled trial is currently underway in renal transplant patients with a novel vaccine based on a backbone of lymphocytic choriomeningitis virus and the results are awaited with interest (NCT03629080).…”