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Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis

Anette Stryhn^2,

Allan Randrup Thomsen^2,

Peter J. M. Openshaw^1,

¹ Department of Respiratory Medicine, Imperial College, St Mary's Campus, Norfolk Place, Paddington, London W2 1PG, UK
² Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark

Correspondence
Peter J. M. Openshaw
p.openshaw{at}imperial.ac.uk

A CD8⁺ T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant K^d-restricted epitope from the viral transcription anti-terminator protein M2 (M2_82–90), linked covalently to human ₂-microglobulin (₂m). Cutaneous gene-gun immunization of BALB/c mice with this construct induced an antigen-specific CD8⁺ T-cell memory. After intranasal RSV challenge, accelerated CD8⁺ T-cell responses were observed in pulmonary lymph nodes and virus clearance from the lungs was enhanced. The construct induced weaker CD8⁺ T-cell responses than those elicited with recombinant vaccinia virus expressing the complete RSV M2 protein, but stronger than those induced by a similar DNA construct without the ₂m gene. DNA vaccination led to enhanced pulmonary disease after RSV challenge, with increased weight loss and cell recruitment to the lung. Depletion of CD8⁺ T cells reduced, but did not abolish, enhancement of disease. Mice vaccinated with a construct encoding a class I-restricted lymphocytic choriomeningitis virus epitope and ₂m suffered more severe weight loss after RSV infection than unvaccinated RSV-infected mice, although RSV-specific CD8⁺ T-cell responses were not induced. Thus, in addition to specific CD8⁺ T cell-mediated immunopathology, gene-gun DNA vaccination causes non-specific enhancement of RSV disease without affecting virus clearance.

Present address: T-cellic, Hoersholm, Denmark.

These authors contributed equally to this work.

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