@article{mbs:/content/journal/jgv/10.1099/vir.0.80098-0, author = "Bartholdy, Christina and Olszewska, Wieslawa and Stryhn, Anette and Thomsen, Allan Randrup and Openshaw, Peter J. M.", title = "Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis", journal= "Journal of General Virology", year = "2004", volume = "85", number = "10", pages = "3017-3026", doi = "https://doi.org/10.1099/vir.0.80098-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.80098-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "A CD8+ T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant Kd-restricted epitope from the viral transcription anti-terminator protein M2 (M282–90), linked covalently to human β 2-microglobulin (β 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 β 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 β 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.", }