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

Rapidly protective MVA immunization in the absence of B cells Previous work had already indicated that adaptive immunity contributes to MVA-induced protection against lethal ECTV infection [41] . Furthermore, passive immunization with vaccinia immune globulin around the day of infection fully protects mice against lethal mousepox [53] , indicating that antibodies are the important players in adaptive immunity. Indeed, we showed above that specific antibodies are found in the respiratory tract early after intranasal inoculation with MVA ( Figure 1D ). To further analyze the role of antibody responses we performed experiments to assess the rapid protective capacity of MVA vaccination in RAG-1 2/2 mice lacking mature T and B cells, and in B cell-deficient mMT mice [54] . Confirming previous data, vaccinated RAG-1 2/2 mice ( Figure 3A ) all succumbed to the ECTV challenge infection, confirming the importance of adaptive responses in rapid protection. However, MVA immunization robustly protected B cell-deficient mice from disease and death ( Figure 3B ; P,0.0001).