1887

Abstract

A CD8 T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant K-restricted epitope from the viral transcription anti-terminator protein M2 (M2), linked covalently to human -microglobulin ( m). 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 m 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 m 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.

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2004-10-01
2020-07-11
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