MVA was chosen as the poxvirus vector to boost immunity induced by GeoVax's DNA priming vaccination because of its safety features and the excellent protective responses it stimulated in preclinical (primate) models.
MVA was originally developed as a safe smallpox vaccine for use in immuno-compromised humans by further attenuating the standard smallpox vaccine. During this attenuation (loss of disease causing ability), MVA also lost essentially all of its ability to replicate in human cells. The attenuation was accomplished by making over 500 passages of the virus in chicken embryos or chick embryo fibroblasts (CEF). During passage the virus underwent 6 large genomic deletions. These deletions affected the ability of MVA to replicate and cause safety problems in humans. However, it did not compromise the ability of MVA to grow on the CEF cells that are required for manufacturing the virus.
The effectiveness of MVA as a vaccine vector is also enhanced by its loss of immune evasion genes during passages in CEF cells. Throughout the years of the dreaded human smallpox epidemics, immune evasion genes assisted the spread of smallpox infections even with the presence of human immune responses.
MVA was safely administered to over 120,000 people in the 1970's to protect them against smallpox. With the advent of bioterrorism, our choice of the MVA vector has become even more important. GeoVax's AIDS vaccines may ultimately serve a dual purpose - protection against AIDS as well as smallpox.