Gene-based vaccine approaches for respiratory syncytial virus

A respiratory syncytial virus (RSV) vaccine has remained elusive for decades, largely due to the failure of a formalin-inactivated RSV vaccine in the 1960s that resulted in enhanced disease upon RSV exposure in the immunized individuals. Vaccine development has also been hindered by the incomplete immunity conferred by natural infection allowing for re-infection at any time, and the immature immune system and circulating maternal antibodies present in the neonate, the primary target for a vaccine. This chapter will review the use of gene delivery, both nonviral and viral, as a potential vaccine approach for human RSV. Many of these gene-based vaccines vectors elicit protective immune responses in animal models. None of the RSV gene-based platforms have progressed into clinical trials, mostly due to uncertainty regarding the direct translation of animal model results to humans and the hesitancy to invest in costly clinical trials with the potential for unclear and complicated immune responses. The continued development of RSV vaccine gene-based approaches is warranted because of their inherent flexibility with regard to composition and administration. It is likely that multiple candidate vaccines will reach human testing in the next few years.