The mechanism of immune protection is poorly understood, in part because immunology was in its infancy when smallpox was eradicated by the widespread application of the Dryvax^® vaccine. Dryvax^®, the vaccinia (smallpox) vaccine currently licensed in the United States, is a lyophilized, live-virus preparation of infectious vaccinia virus. Vaccinia vaccine does not contain smallpox (variola) virus. Vaccinations against the disease have not been required in the United States since 1972.

“This study provides a better understanding of the mechanism of vaccine protection against vaccinia virus infection and may provide insights for further vaccine developments against smallpox.”

Both virus-specific antibody and CD8 CTL have been thought to play a role in protection against orthopoxviruses. However, the mechanism of protection against pathogenic vaccinia virus has not been systematically studied by currently available techniques. The licensed smallpox vaccine, Dryvax^®, can be considered very risky to immunize the population that is immunocompromised by AIDS, chemotherapy for cancer, or immunosuppression following organ transplant. Therefore, a second-generation smallpox vaccine is needed. The urgency for development of a new, more effective vaccine against smallpox is increased today because of concern about bioterrorism.

In this study, we demonstrated that neither CD4 nor CD8 effector T cells were necessary or sufficient to protect mice against pathogenic vaccinia virus, whereas an antibody response—which depends on CD4+ Thelp for its induction—was sufficient. Vaccinia-specific CD4 and CD8 cells prevented mortality of infected immunized mice. T cell immunity was important for natural resistance against poxvirus in naïve mice. We discovered that the same types of responses contributed to protection by both modified vaccinia Ankara (replication-deficient vaccinia) and licensed Wyeth strains of vaccinia virus, making comparison of these by surrogate immune response markers feasible.

Our paper is highly cited because this study can help in the development of a better vaccine against smallpox, and, in particular, provide a basis for further evaluation of replication-deficient vaccinia viruses as safer vaccines against smallpox. Our work helped resolved a contentious issue, namely what immune mechanisms are important for protection against pathogenic vaccinia.

This study provides a better understanding of the mechanism of vaccine protection against vaccinia virus infection and may provide insights for further vaccine developments against smallpox.

This paper describes the importance of different immune mechanisms for protection against poxviruses (including smallpox) in immunized and unimmunized animals. We demonstrated that, at sufficient doses, protection can be provided by attenuated vaccinia virus as well.

Our interest in viral immunology is longstanding. However, this study was possible because of our collaboration with Dr. Bernard Moss and his lab (Lab of Viral Diseases, NIAID, NIH, DHHS).

Yes, primarily because of national and international concerns about bioterrorism.