Vaccinia viruses: vaccines against smallpox and vectors against infectious diseases and tumors

Abstract

Less than 200 years after its introduction, widespread use of vaccinia virus (VACV) as a smallpox vaccine has eradicated variola virus. Along with the remarkable success of the vaccination program, frequent and sometimes severe adverse reactions to VACV were encountered. After eradication, VACV has been reserved for select populations who might be at significant risk for orthopoxvirus infections. Events over the past decade have renewed concerns over the potential use of variola virus as a biological weapon. Accordingly, interest in VACV and attenuated derivatives has increased, both as vaccines against smallpox and as vectors for other vaccines. This article will focus on new developments in the field of orthopoxvirus immunization and will highlight recent advances in the use of vaccinia viruses as vectors for infectious diseases and malignancies.

Figure 1. Clinical take response correlates with viral titer after scarification

Representative usual take responses are shown from two placebo recipients (A & B) and a blunted take from a subject who received two doses of MVA at 10⁸ sc. (C) as part of a clinical trial with MVA [72]. Subjects who elected to receive scarification with Dryvax were followed for clinical take, graded as 3 (normal take), 2 (reduced take), or 1 (limited take) based on CDC criteria and correlated with progency viral shedding [88]. Photographs courtesy of Lindsey R Baden and Marissa A Wilck.