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* Department of Microbiology and
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242
Vaccination of children with a formalin-inactivated (FI) respiratory syncytial virus (RSV) vaccine led to exacerbated disease including pulmonary eosinophilia following a natural RSV infection. Immunization of BALB/c mice with FI-RSV or a recombinant vaccinia virus (vv) expressing the RSV attachment (G) protein (vvG) results in a pulmonary Th2 response and eosinophilia after RSV challenge that closely mimics the RSV vaccine-enhanced disease observed in humans. The underlying causes of RSV vaccine-enhanced disease remain poorly understood. We demonstrate here that RSV M2-specific CD8 T cells reduce the Th2-mediated pathology induced by vvG-immunization and RSV challenge in an IFN-
-independent manner. We also demonstrate that FI-RSV immunization does not induce a measurable RSV-specific CD8 T cell response and that priming FI-RSV-immunized mice for a potent memory RSV-specific CD8 T cell response abrogates pulmonary eosinophilia after subsequent RSV challenge. Our results suggest that the failure of the FI-RSV vaccine to induce a CD8 T cell response may have contributed to the development of pulmonary eosinophilia and augmented disease that occurred in vaccinated individuals.
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 National Institutes of Health Grant AI 063520, American Heart Association Heartland Affiliate Beginning Grant-in-Aid 0615625Z (to S.M.V.), and National Institutes of Health Training Grant T32AI007533 (to M.R.O.).
2 Address correspondence and reprint requests to Dr. Steven 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, bronchial alveolar lavage; 
-gal, -galactosidase; F, fusion; GKO, IFN- deficient; FI-RSV, formalin inactivated-RSV; ICS, intracellular cytokine staining; vv, vaccinia virus; WT, wild type.
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