Characterization of the proliferative response to the smallpox vaccine in human immune PBMC

Vaccination against variola virus, credited to Edward Jenner in the late 18th century, helped to eradicate smallpox from the world. Since its eradication, the study of this disease and its pathology was given little attention; however, with the emergence of monkeypox virus into the human population and the potential use of smallpox as a bioterrorist weapon, the need to vaccinate the world's population is once again a reality. The vaccines used during the eradication program were live, attenuated vaccinia virus preparations of varying virulence that caused a significant number of adverse reactions in naive subjects. Currently, immunosuppressed individuals, persons with certain skin diseases, and people with cardiovascular complications are contraindicated against receiving this type of vaccine. A new vaccine is needed. Until now, the only known correlate of immunity to the smallpox vaccine conveying protection is the development of a scar at the site of vaccination. Characterizing the immune response established upon vaccination with Dryvax RTM, at both the innate and adaptive levels, would greatly enhance our understanding of the human immune response to the vaccine, and thus generate information for the evaluation of new and safer next-generation vaccines. In the studies presented here, we show that the ex vivo proliferative response to VACV is comprised of several cell types, (including CD4+ T cells, CD8+ T cells, gammadelta-T cells, NK cells and NKT cells), and that the entire proliferative response is dependent on CD4+ T cells. These studies characterize the VACV-induced ex vivo proliferative response in immune individuals and would serve as a beneficial additional immunological parameter for comparing the immunogenicity of next-generation vaccines to that of DryvaxRTM. In addition, these studies argue for a more thorough analysis of the role of CD4+ T helper cells in the recall proliferative response to VACV.