Live Viral Vectors: Semliki Forest Virus

A continuously expanding body of data supports the use of recombinant viral vectors as vehicles in vaccination. Studies have shown that when antigen-expressing viral vectors are used alone or in boosting following a naked DNA prime, the T- and B-cell responses elicited are both broader and of a higher order of magnitude than following immunization with DNA alone (1 –6 ). The mechanisms underlying the efficiency of live viral vectors probably lie in their replicative nature. Although in most cases the vectors are attenuated or “suicidal,” resulting in nonproductive infections (e.g., no spread of progeny virus in the vaccinee), the vectors replicate inside the target cell, mimicking an authentic virus infection and resulting in the activation of innate anti-viral responses in the antigen-expressing cell. Live viral vectors thus come with built-in immuno-stimulatory properties much like a live attenuated virus vaccine, giving these platforms an advantage over strategies using conventional plasmid DNA to express antigen. Another characteristic of many viral vaccine vectors is that they induce apoptosis in the target cell. This may contribute to the generation of a specific immune response caused by uptake of antigen-loaded apoptotic bodies by dendritic cells and consequent activation of a specific response through cross-presentation. Further studies are required to formally demonstrate to what extent such mechanisms contribute to the activity of live viral vectors. It will be important to learn more about how the different viral vectors work in relation to each other and what other mechanisms are involved.