A phase I trial of Epstein Barr virus gp350 vaccination for children awaiting renal transplantation

Children undergoing solid organ transplantation are at risk of developing lymphoproliferative disease for which peri-transplant primary infection with Epstein-Barr virus (EBV) is the major risk factor. The clinical pattern ranges from infectious mononucleosis to lymphoma. Transmission is via infectious virions normally in saliva but also released from EBV-infected B cells transferred with the donor organ. Viral gp350 and host CD21 interactions mediate B cell infection. In a proof of mechanism trial, we sought to establish whether vaccination with recombinant gp350 with 0.2% alhydrogel would result in anti-gp350 antibody responses in EBV-negative children awaiting renal transplantation and negative for EBV. Five subjects (aged 1-14 years) received three 12.5mcg vaccinations over 9 weeks. Ten subjects were vaccinated with 25mcg, receiving two (n=2) or three (n=8) doses over 9 weeks, of whom 3 received an additional booster dose at weeks 26-28. gp350-specific antibodies were present in all subjects by week 7-10 having been negative before the first injection. The fourth booster significantly increased responses measured at weeks 32-34. EBV neutralising antibodies were detected in 2/5 and 6/10 patients in the two cohorts. Vaccination was generally well tolerated and dose limiting toxicity not observed. Injection site reactions were the main toxicity: one patient withdrew because of this. One patient had systemic symptoms following the first vaccination but did not withdraw. These data will be used to design a proof of principle phase II trial to determine the whether gp350 vaccination modifies subsequent EBV infection.