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

The most effective approach to prevent infectious diseases caused by viruses is vaccination. During the period of rational vaccine development, immunogenicity and the efficacy of vaccines were evaluated in terms of their ability to induce virus-specific antibodies. More recently however, the focus has shifted to considering the importance of cellular immune responses. In fact, vaccine-induced T cell immunity might be crucial to overcome some viral diseases. Viruses such as influenza virus or HIV are highly versatile in changing their envelope antigens to escape the host antibody response. Thus, induction of robust T cell immunity is believed to be the key to achieving successful immunization against AIDS, or enabling cross-protective capacities in next generation influenza vaccines [1] [2] [3] . Moreover, T cells are being recognized as playing an important role in the control of certain viral infections such as human cytomegalovirus diseases [4, 5] . Surprisingly however, there is very limited data about the contribution of T cell immunity to protection provided by any licensed viral vaccine. Even today, as in the case of influenza vaccines, most applications for marketing approval only assess the potency and efficacy of candidate vaccines using antibody correlates [6] [7] [8] . Moreover, regarding the immunological requirements for protective vaccination at times close to viral infection our knowledge is very limited, perhaps with exception of rabies where antibodies induced by post exposure vaccination are well known to prevent the disease and death [9, 10] .