Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Adult Hematopoietic Cell Transplant Recipients: A Single Center Study

Abstract

<h3>Background</h3> Hematopoietic cell transplant (HCT) recipients are at high risk for Varicella zoster virus (VZV) reactivation. Shingrix, the adjuvanted recombinant zoster vaccine, is a new alternative to the live-attenuated VZV vaccine for immunocompromised individuals. Post-marketing data on its immunogenicity and safety in HCT is limited. <h3>Objectives</h3> To assess the safety and immunogenicity of Shingrix vaccine in HCT recipients. <h3>Methods</h3> Single center retrospective study of 134 consecutive adult allogenic and autologous HCT recipients who received the full series (two doses) of Shingrix vaccine. Primary study end points were safety and immunogenicity defined as either seroconversion in previously seronegative individuals or 4-fold increase from baseline VZV IgG titers in previously exposed patients. <h3>Results</h3> Among the 134 patients who completed vaccine series, 39 patients including 25 allogeneic and 14 autologous HCT recipients (Figure), had serological data available at baseline and after completion of vaccine series. The median age of patients at the time of HCT was 61 years (IQR, 53-67). The median time from HCT to first dose of Shingrix vaccine was 9 months (IQR, 7-14) for the entire cohort, but it was significantly shorter in autologous versus allogeneic HCT recipients: 7 (IQR, 6-8) vs. 12 (IQR, 9-16) months (P=0.003 by Mann Whitney test), respectively. Vaccine administration was very well tolerated, out of 134 patients only two (1.4%) had documented adverse events following Shingrix (and other vaccines co-administered), including injection site reaction after second dose and flu-like syndrome with fatigue and non-productive cough after the first dose (n=1 each). Both reactions occurred in autologous HCT recipients. The median time from the second Shingrix dose to post-vaccination VZV IgG titer assessment was 3.5 (IQR, 2-6) months. A total of 16 (41%) patients had documented humoral vaccine responses as measured by post vaccination VZV IgG levels including 8/14 (57%) autologous HCT recipients compared to 8/25 (32%) allogeneic HCT recipients (P=0.18 by Fisher's exact test). Among the 16 responders, the VZV IgG antibody concentration index increased from 179 (2.1-559) to 3,868 (2,232-4,000) (P<0.0001 by Wilcoxon matched-pairs signed rank test). Of interest, 100% of the patients who were seronegative prior to vaccination (n=8) seroconverted in response to Shingrix. <h3>Conclusions</h3> A 2-dose course of adjuvanted recombinant zoster vaccine was well tolerated among adult HCT recipients. Vaccine humoral responses occurred in less than half of the patients although vaccine seems to be more immunogenic following autologous HCT and among seronegative patients. Although Shingrix vaccine is currently only licensed for VZV seropositive patients, our data indicate that this recombinant vaccine may also be useful for primary VZV immunization. Larger studies are needed.