Inactivation of the viral interleukin 1β receptor improves CD8+ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara Staib, Caroline and Kisling, Sigrid and Erfle, Volker and Sutter, Gerd,, 86, 1997-2006 (2005), doi = https://doi.org/10.1099/vir.0.80646-0, publicationName = Microbiology Society, issn = 0022-1317, abstract= Interleukin 1 (IL1) is an important regulator of inflammatory responses and contributes to host immune defence against infection. Vaccinia virus encodes a viral soluble IL1β receptor (IL1βR), 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 IL1βR production were produced by insertion of selectable marker gene sequences that precisely deleted the IL1βR coding sequences from the MVA genome (MVA-ΔIL1βR). Analysis of MVA mutants indicated that deletion of the IL1βR gene did not abrogate the formation of MVA progeny upon tissue culture propagation. After high-dose intranasal infection with MVA-ΔIL1βR, mice showed no signs of fever or other illness, suggesting that the avirulent phenotype remained preserved for MVA-ΔIL1βR. Following vaccination of mice, MVA-ΔIL1βR 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-ΔIL1βR. Moreover, 4–6 months after vaccination, MVA-ΔIL1βR 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 IL1βR 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., language=, type=