Herpes simplex virus (HSV) 1 and 2, varicella zoster virus (VZV), and human herpesvirus 6 (HHV-6) cause severe infections in immunocompromised hosts. Interventions to optimize virus-specific adaptive immunity may have advantages over antivirals in the prophylaxis and treatment of these infections.
We sought to review adaptive immune responses and methods for assessing and replenishing cellular and humoral immunity to HSV, VZV and HHV-6 in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients.
We searched PubMed for relevant studies on immune responses to HSV, VZV and HHV-6 as well as studies describing methods for evaluating and restoring cell-mediated immunity to other double stranded DNA viruses in transplant recipients. Recent studies, randomized controlled trials, and investigations highlighting key concepts in clinical virology were prioritized for inclusion.
We describe the mechanisms of adaptive immunity to HSV, VZV and HHV-6, and limitations of antivirals as prophylaxis and treatment for these infections in SOT and HCT recipients. We review methods for measuring and restoring cellular immunity to double stranded DNA viruses, their potential applications to management of HSV, VZV, and HHV-6 in immunocompromised hosts, and barriers to clinical use. Vaccination and virus-specific T cell therapies are discussed in detail.
The growing repertoire of diagnostic and therapeutic techniques focused on virus-specific adaptive immunity provides a novel approach to management of viral infections in transplant recipients. Investigations to optimize such interventions specifically in HSV, VZV, and HHV-6 are needed.

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