Background/Purpose: SLE patients have increased risk of Herpes Zoster (HZ).  A live-attenuated vaccine is available for healthy persons > 50 years old, but its safety in immunocompromised individuals is unknown.  Two areas of possible concern regard the development of vaccine-induced HZ, and increased disease activity following stimulation from an immunogenic vaccine. We sought to evaluate gene expression profiles between SLE patients and healthy controls after VZV vaccination to identify any potential increase in immune system activation or impaired viral control in SLE patients.

Methods: We performed a pilot open-label study of HZ vaccine in 10 SLE patients with low disease activity and 10 healthy, matched controls.   Safety outcomes included vaccine-induced HZ or flare of underlying SLE following vaccination. Whole-blood RNA was collected in Tempus tubes to study early changes in immune related pathways at baseline and 2 weeks post-vaccination in a subset of 5 matched pairs of SLE patients and controls.  RNA-sequencing was done using an Illumina HiSeq 2000 with the resulting FASTQ files aligned to the human genome using STAR.  DEseq was used to determine differential expression with the threshold of P<0.01 and fold change (FC) >2 or <0.5.

Results: No subjects developed vaccine-induced HZ during the 12 weeks of the study.  SLE patients had quiescent disease at baseline, and no clinical flares were noted. When comparing the baseline samples of the SLE cases to the healthy controls, we identified 107 differentially expressed genes including several that are known to be type I interferon (T1IFN)-inducible (OAS1, OAS2, OAS3, MX1, IFIH1, IFIT2, IFIT3, among others).  These genes mapped to pathways involved in response to virus (P=8.08x10E-20), immune response (P=1.15x10E-16), and T1IFN-mediated signaling pathway (P=7.17x10E-16), among others.  The analysis of the 14-day post-vaccination visits between SLE case and healthy controls yielded only 37 differently expressed genes.  Although some of the same T1IFN-inducible genes were differently expressed (e.g. OAS3, MX1, IFIT2, IFIH1), we observed a statistically significant reduction in the number of T1IFN-inducible genes between the baseline and the post vaccination analyses (P=0.005).  Moreover, a statistically significant reduction was observed in the FC between the differentially expressed genes that overlapped between the baseline and post-vaccination analyses (P=8.34x0E-7).  No evidence of HZ viral gene expression was detected in either the cases or controls.

Conclusion: In this pilot study of quiescent SLE patients, HZ vaccine did not lead to clinical flares, nor increased evidence of systemic inflammation or autoimmunity.  HZ viremia was not detected. At baseline, differences in gene expression between SLE patients and controls were consistent with other studies of SLE.  Changes observed in expression profiles 14 days post-vaccination suggests that the controls have responded to the vaccine and have become more similar to the SLE cases.  Future studies with larger samples sizes are needed to determine true flare rates and gage any differences in immune response to vaccine in those patients for whom vaccine might be associated with flare.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rna-sequencing-confirms-clinical-safety-of-herpes-zoster-vaccine/