acute reactogenicity after intramuscular immunization with recombinant vesicular stomatitis virus is linked to production of il-1β急性肌内免疫接种后不良反应与重组水泡性口炎病毒与il-1β的生产.pdfVIP

Acute Reactogenicity after Intramuscular Immunization with Recombinant Vesicular Stomatitis Virus Is Linked to Production of IL-1b Kathleen Athearn1,2,3, Christopher J. Sample1,2, Brice E. Barefoot1,2, Kristi L. Williams2,4., 1,2,3 . Elizabeth A. Ramsburg * 1 Human Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, United States of America, 2 Department of Medicine, School of Medicine, Duke University, Durham, North Carolina, United States of America, 3 Department of Pathology, School of Medicine, Duke University, Durham, North Carolina, United States of America, 4 School of Nursing, School of Medicine, Duke University, Durham, North Carolina, United States of America Abstract Vaccines based on live viruses are attractive because they are immunogenic, cost-effective, and can be delivered by multiple routes. However, live virus vaccines also cause reactogenic side effects such as fever, myalgia, and injection site pain that have reduced their acceptance in the clinic. Several recent studies have linked vaccine-induced reactogenic side effects to production of the pro-inflammatory cytokine interleukin-1b (IL-1b) in humans. Our objective was therefore to determine whether IL-1 b contributed to pathology after immunization with recombinant vesicular stomatitis virus (rVSV) vaccine vectors, and if so, to identify strategies by which IL-1 b mediated pathology might be reduced without compromising immunogenicity. We found that an rVSV vaccine induced local and systemic production of IL-1b in vivo, and that accumulation of IL-1b correlated with acute pathology after rVSV immunization. rVSV-induced pathology was reduced in mice deficient in the IL-1 rec