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Cutting Edge: Eosinophils Do Not Contribute to Respiratory Syncytial Virus Vaccine-Enhanced Disease¹

Elaine M. Castilow^*, Kevin L. Legge^*, and Steven M. Varga^2,*,

^* Interdisciplinary Graduate Program in Immunology, Department of Pathology, and Department of Microbiology, University of Iowa, Iowa City, IA 52242

Respiratory syncytial virus (RSV) infection of BALB/c mice previously immunized with a recombinant vaccinia virus (vacv) expressing the attachment (G) protein of RSV (vacvG) results in pulmonary eosinophilia, which mimics the response of formalin-inactivated RSV-vaccinated children, as well as increased weight loss, clinical illness, and enhanced pause (Penh). We show that RSV infection of eosinophil-deficient mice previously immunized with vacvG results in the development of increased weight loss, clinical illness, and Penh similar to that in wild-type controls. These measures of RSV vaccine-enhanced disease are dependent upon STAT4. Interestingly, neither IL-12 nor IL-23, the two most common STAT4-activating cytokines, proved necessary for the development of disease. We demonstrate that IFN-, which is produced following STAT4 activation, contributes to clinical illness and increased Penh, but not weight loss. Our results have important implications for future RSV vaccine design, suggesting that enhancing a Th1 response may exacerbate disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by funding by American Heart Association Midwest Affiliate Predoctoral Fellowship 0815540G (to E.M.C.), Department of Pathology Start-Up Funds (to K.L.L.), and National Institutes of Health Grant AI 063520 (to S.M.V.).

² Address correspondence and reprint requests to Dr. Steven M. Varga, Department of Microbiology, 51 Newton Road, University of Iowa, Iowa City, IA 52242. E-mail address: steven-varga{at}uiowa.edu

³ Abbreviations used in this paper: RSV, respiratory syncytial virus; BAL, bronchoalveolar lavage; FI, formalin inactivated; Penh, enhanced pause; vacv, vaccinia virus; vacvG, vacv expressing RSV attachment (G) protein; vacvβ-gal, vacv expressing β-galactosidase; WT, wild type; KO, knockout.

⁴ The online version of this article contains supplemental material.

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