Safety of vaccinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation

Abstract

Reactivation of varicella zoster virus (VZV), clinically manifested as herpes zoster (HZ) is a common complication after hematopoietic stem cell transplantation (HSCT). The optimum prophylaxis for this disease has not been defined. In this study, we examined the effects of vaccinating donors with a live-attenuated vaccine with particular reference to their immune responses and the outcome of HSCT patients. Forty prospective HLAmatched sibling donors were vaccinated before HSCT. There were humoral immune responses in both seropositive (Po0.01) and sero-negative (P ¼ 0.058) donors. Cellular immune response was assayed in 26 donors. Significant correlation was observed between cellular immune responses as enumerated by thymidine incorporation and interferon c secretion (Po0.001) and the latter was used in subsequent analyses. Significant response was observed in sero-negative (6/26) and a group of seropositive (13/26) donors while 7/26 sero-positive donors showed no response. Thirty-four HSCT were performed. These patients have a lower, albeit insignificant, risk of HZ compared with historical controls and only 3/34 patients developed single dermatomal HZ at 6, 9 and 28 months after HSCT. No patients developed VZV-related mortality. Vaccinating donors with live-attenuated VZV vaccine was safe, but whether it confers a significant protection to the patients would require further study.

Looking back to move forward: a twenty-year audit of herpes zoster in Asia-Pacific

“…HZ is a very common complication following HSCT [170, 774]. Long-term prophylaxis with low-dose aciclovir [775–778] or valaciclovir [779] significantly reduces the incidence of VZV reactivation and serious complications, and is recommended for the duration of immunotherapy and continuing through 1 year after HSCT [776, 778].…”

“…A case of recurrent HZO cured by varicella vaccination was also reported [786]. In studies that evaluated live-attenuated VZV vaccine in HSCT [774, 787], Oka/RIT (Varilrix™ Glaxo-SmithKline Biologicals, Rixensart, Belgium) was safe but poorly immunogenic. A systematic review concluded that although inactivated VZV vaccine may reduce HZ severity in stem cell transplant recipients, more research was required [788].…”

Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia

“…133 Although initial reports of the administration of heatinactivated live attenuated varicella vaccine to SCT recipients were encouraging, 134,135 this approach has not yet been further developed.…”

Clinical Evaluation of Safety and Immunogenicity of PADRE-Cytomegalovirus (CMV) and Tetanus-CMV Fusion Peptide Vaccines With or Without PF03512676 Adjuvant

“…Our strategy is to provide sufficient CMV immunity to HCT recipients by vaccinating their immunocompetent donors [18][19][20]. Studies have shown that by immunizing the donor pre-HCT, it is possible to transfer vaccine-specific immunity to the recipient [20][21][22][23].…”