Critical Role of Perforin-dependent CD8+ T Cell Immunity for Rapid Protective Vaccination in a Murine Model for Human Smallpox

Kremer, Melanie; Suezer, Yasemin; Volz, Asisa; Frenz, Theresa; Majzoub, Monir; Hanschmann, Kay-Martin; Lehmann, Michael H.; Kalinke, Ulrich; Sutter, Gerd

Vaccination is still the most successful approach to prevent viral diseases. The recent threats of suddenly emerging severe infectious diseases, e.g. caused by severe acute respiratory syndrome coronavirus, West Nile virus, or avian influenza virus, demonstrate the need for new vaccines ready to use in an immediate public health response. Previous studies in animal models for preventing fatal orthopoxvirus disease had shown that immunizations with MVA or conventional VACV could provide protection in a time window close to lethal infection [39, 41, 43] . The purpose of the present study was to determine the immunological mechanisms mediating this rapid protective capacity of MVA vaccination in an orthopoxvirus infection model. Previous studies in the mousepox model had shown that pre-and post-exposure protection can be achieved, and suggested that the induction of adaptive immune responses was essential [41, 42] . Post-exposure immunizations, in particular when given at later times (e.g. 2 days post ECTV infection), can not prevent the onset of severe mousepox disease [41] . However, this feature clearly hampers the definition of immune correlates for MVA vaccine mediated rapid protection (our unpublished data) [63] . In contrast, MVA vaccination two days prior to lethal ECTV challenge allows for solid protection also against the onset of morbidity. Therefore, we chose the preexposure immunization model for this study.