The future of respiratory syncytial virus vaccine development

Background. Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract illness in infants and children and is an important cause of lower respiratory tract illness in other populations. Despite decades of research there are currently no licensed vaccines for prevention of RSV disease. Methods. A review of the obstacles to RSV vaccine development; current live, attenuated and subunit RSV vaccines in clinical development; and the potential for developing additional vaccine candidates based on recombinant technology. Results. A number of biologically derived live attenuated RSV vaccines were evaluated in Phase I clinical trials in adults and children, and one vaccine (cpts 248/404) was evaluated in infants as young as 1 month of age. These vaccines displayed a spectrum of attenuation, with cpts 248/955 being the least attenuated and epts 248/404 being the most attenuated candidate vaccine. None of these was sufficiently attenuated for young infants. The ability to generate recombinant RSV vaccines has led to the development of large numbers of candidate vaccines containing combinations of known attenuating point mutations and deletions of nonessential genes. Clinical evaluation of many of these candidates is in progress. Three types of RSV subunit vaccines have recently been evaluated in clinical trials: purified F glycoprotein vaccines (PFP-1, PFP-2 and PFP-3), BBG2Na and copurified F, G and M proteins. Additional studies of the F/G/M protein vaccine are being conducted. Conclusions. During the past 10 years, considerable progress has been made in RSV vaccine development. It is likely that different RSV vaccines will be needed for the various populations at risk.