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

Here, we used ectromelia virus (ECTV) infections of mice, probably the best surrogate animal model for human smallpox. Our aim was to analyze the immunological mechanism(s) of the early protective capacity conferred by MVA immunization. Surprisingly, we found that rapid protection against lethal systemic poxvirus disease, as mediated by vaccination with MVA or conventional VACV, is solely dependent on the cellular adaptive immune response with an important role of CD4 and CD8 T cells, and perforin mediated cellular cytotoxicity. In contrast, the humoral response seems to be fully dispensable in providing early protection. Our data clearly demonstrate that T cell immunity plays a key role in the protective capacity of vaccination with a gold standard live viral vaccine. In general, the rapid induction of robust T cell responses might be of great importance for developing vaccines that need to meet the demands of protective emergency vaccination.