Strategic priorities for respiratory syncytial virus (RSV) vaccine development.

Although RSV has been a high priority for vaccine development, efforts to develop a safe and effective vaccine have yet to lead to a licensed product. Clinical and epidemiologic features of RSV disease suggest there are at least 4 distinct target populations for vaccines, the RSV naïve young infant, the RSV naïve child ≥ 6 months of age, pregnant women (to provide passive protection to newborns), and the elderly. These target populations raise different safety and efficacy concerns and may require different vaccination strategies. The highest priority target population is the RSV naïve child. The occurrence of serious adverse events associated with the first vaccine candidate for young children, formalin inactivated RSV (FI-RSV), has focused vaccine development for the young RSV naïve child on live virus vaccines. Enhanced disease is not a concern for persons previously primed by a live virus infection. A variety of live-attenuated viruses have been developed with none yet achieving licensure. New live-attenuated RSV vaccines are being developed and evaluated that maybe sufficiently safe and efficacious to move to licensure. A variety of subunit vaccines are being developed and evaluated primarily for adults in whom enhanced disease is not a concern. An attenuated parainfluenza virus 3 vector expressing the RSV F protein was evaluated in RSV naïve children. Most of these candidate vaccines have used the RSV F protein in various vaccine platforms including virus-like particles, nanoparticles, formulated with adjuvants, and expressed by DNA or virus vectors. The other surface glycoprotein, the G protein, has also been used in candidate vaccines. We now have tools to make and evaluate a wide range of promising vaccines. Costly clinical trials in the target population are needed to evaluate and select candidate vaccines for advancement to efficacy trials. Better data on RSV-associated mortality in developing countries, better estimates of the risk of long term sequelae such as wheezing after infection, better measures of protection in target populations, and data on the costs and benefits of vaccines for target populations are needed to support and justify funding this process. Addressing these challenges and needs should improve the efficiency and speed of achieving a safe and effective, licensed RSV vaccine.