Journal
JOURNAL OF GENERAL VIROLOGY
Volume 86, Issue -, Pages 1997-2006Publisher
MICROBIOLOGY SOC
DOI: 10.1099/vir.0.80646-0
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Interleukin 1 (IL1) is an important regulator of inflammatory responses and contributes to host immune defence against infection. Vaccinia virus encodes a viral soluble IL1 beta receptor (IL1 beta R), which modulates the acute-phase host response to infection and might influence the induction of immune responses against virus-associated antigens. Here, modified vaccinia virus Ankara (MVA) mutants defective in IL1 beta R production were produced by insertion of selectable marker gene sequences that precisely deleted the IL1 beta R coding sequences from the MVA genome (MVA-Delta IL1 beta R). Analysis of MVA mutants indicated that deletion of the IL1 beta R gene did not abrogate the formation of MVA progeny upon tissue culture propagation. After high-dose intranasal infection with MVA-Delta IL1 beta R, mice showed no signs of fever or other illness, suggesting that the avirulent phenotype remained preserved for MVA-Delta IL1 beta R. Following vaccination of mice, MVA-Delta IL1 beta R or non-mutated MVA induced similar acute-phase immune responses. Importantly, when monitored at the memory phase, significantly higher vaccinia virus-specific total CD8(+) and HLA-A*0201-binding peptide epitope-specific T-cell responses were found after vaccination of HLA-A*0201-transgenic and non-transgenic mice with MVA-Delta IL1 beta R. Moreover, 4-6 months after vaccination, MVA-Delta IL1 beta R provided higher levels of protection against lethal respiratory challenge infection with virulent vaccinia virus strain Western Reserve compared with wild-type MVA. These data suggest that deletion of the viral IL1 beta R gene may be considered a relevant approach to amplify the virus-specific CD8(+) memory T-cell response and duration of protective immunity obtained after MVA vaccination.
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