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

i.m. MVA immunization using 10 8 PFU ( Figure 8A,B) , as well as with i.d. vaccination with 10 6 PFU of VACV strain Elstree ( Figure 8C ). Previous studies had confirmed the protective capacity of this lower-dose immunization using the fully replication competent VACV Elstree [41] . As expected, control C57BL/6 wt mice were fully protected by vaccination two days prior to the lethal respiratory challenge infection with ECTV (p = 0.006 for MVA i.n.; p = 0.0011 for MVA i.m.; p = 0.005 for VACV Elstree). In sharp contrast, all vaccinated, T cell-depleted animals succumbed to ECTV infection irrespective of vaccination by MVA or VACV Elstree strains or the different routes of immunization. Additionally, the morbidity profiles of T celldepleted, vaccinated animals were comparable to mock-vaccinated controls (p = 1 for MVA i.n.; p = 0.3489 for MVA i.m.; p = 1 for VACV Elstree i.d.). Furthermore, the protective capacity of MVA vaccination was lost when i.m. inoculating heat-inactivated MVA doses (corresponding to 10 8 PFU) ( Figure S9 ) suggesting the need to immunize live MVA vaccine. These data clearly suggest an essential general requirement for both CD8+ and CD4+ T cells in rapidly protective immunization against fatal mousepox.