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

Intranasal immunizations with VACV are being increasingly investigated as a means to induce immunity associated with the respiratory tract or mucosal tissues. Such applications might be useful in swift mass vaccinations to help overcome major challenges in public health interventions. However, almost all immunizations with VACV in humans, e.g. with the widely used smallpox vaccine strains Lister/Elstree and New York City Board of Health, involved intradermal (i.d.) application through scarification [11] . Clinical uses of MVA-based vaccines routinely choose intramuscular (i.m.) or subcutaneous applications. To elucidate the role of T cells in the rapid protective capacity induced by more conventional vaccination, we again depleted C57BL/6 mice of CD4+ and CD8+ T cells by specific antibodies at the time point of immunization ( Figure S6B ,C). The rapid protective capacity of i.n. MVA immunization was compared with group). +indicate the individual time of death. Error bars indicate SEMs, and the numbers of surviving/total animals are given in parentheses. Data are representative of two or three similar experiments. Statistical significance of differences between groups is indicated by * for p-value,0.05, ** for pvalue,0.01 and *** for p-value,0.001. doi:10.1371/journal.ppat.1002557.g003