Acute Pathogenesis of Recombinant Vesicular Stomatitis Virus Vaccine Vectors is Linked to Interleukin-1

Loading...
Thumbnail Image

Date

2011

Authors

Athearn, Kathleen Constance

Advisors

Ramsburg, Elizabeth

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

397
views
396
downloads

Abstract

Recombinant vesicular stomatitis virus (rVSV) is a promising candidate viral vaccine vector for use in humans. VSV is highly immunogenic, pre-existing immunity to VSV is rare, and VSV is able to grow to high titers in cell lines approved for vaccine use. Its potential reactogenicity is a barrier to its use in humans, with small laboratory animals developing fever and losing up to 20% of their pre-immunization body weight in the first four days after administration [1, 2], and the one person to date that has received an experimental rVSV vaccine developed headache, fever, and muscle pain within 12 hours and transient VSV viremia was detected [3]. The underlying cause of these reactions has not yet been studied. Here, we have found that IL-1β and/or IL-1α contributes to rVSV pathology after intramuscular immunization in mice and that IL-1 production is not required for control of rVSV replication in vivo, or for the generation of protective immune responses to VSV antigens. Suppression of IL-1 may be a safe strategy to reduce vector reactogenicity without affecting immunogenicity. Utilizing mice deficient in either ASC or caspase-1, we have also found that production of mature IL-1β in response to rVSV might be independent of inflammasome activation or caspase-1 cleavage. The exact mechanism is yet to be determined, but might depend upon which cell types secrete mature IL-1β after immunization.

Department

Description

Provenance

Citation

Citation

Athearn, Kathleen Constance (2011). Acute Pathogenesis of Recombinant Vesicular Stomatitis Virus Vaccine Vectors is Linked to Interleukin-1. Master's thesis, Duke University. Retrieved from https://hdl.handle.net/10161/5047.

Collections


Dukes student scholarship is made available to the public using a Creative Commons Attribution / Non-commercial / No derivative (CC-BY-NC-ND) license.