Vaccines Against Respiratory Syncytial Virus: The Time Has Come.

Respiratory syncytial virus (RSV) remains the single most important cause of respiratory tract disease in infants, both in the United States [1] and worldwide [2]. This virus is responsible for bronchiolitis in infants and for clinical disease often indistinguishable from influenza in elderly or immunocompromised hosts. RSV disease was first characterized by astute clinicians such as John Adams in the 1940s, as the cause of primary viral pneumonitis in infants in winter months [3]. RSV was subsequently propagated in Robert Chanock’s laboratory in the late 1950s [4], confirming the laboratory and clinical findings of disease caused by “chimpanzee coryza” virus described earlier by Morris et al in 1956 [5]. Over the next 50 years, innovative clinical studies by Caroline Breese Hall, Paul Glezen, Ann Falsey, and many others demonstrated the ubiquity, importance, and potential severity of RSV infection in preterm infants, young children, immunocompromised patients, and elderly individuals [6–8]. The article by Langley et al [9] in this issue of The Journal of Infectious Diseases adds considerably to our knowledge regarding vaccines against RSV, a saga that has been ongoing for decades with remarkably little success [10]. There is still no approved vaccine against RSV. The tragic outcome of a formalin-inactivated, alum-precipitated RSV vaccine candidate in the 1960s has resulted in a near moratorium on RSV vaccine research since that time [11, 12]. The early formalin-inactivated vaccine candidate not only failed to protect young seronegative infants against RSV disease but resulted in severe enhanced respiratory disease in vaccine recipients after wild-type RSV infection during the subsequent season, with 2 deaths in the vaccine arm [13–16]. In the 1990s, prevention of RSV lower respiratory tract disease with administration of polyclonal immunoglobulin [17] and, subsequently, the humanized monoclonal antibody palivizumab [18] directed against the RSV surface fusion (F) protein were landmark developments in terms of both decreasing severe disease in high-risk infants and advancing the field of RSV research. These prevention studies confirmed earlier work demonstrating that maternally derived RSV antibody was, in fact, protective in infants [19]. The studies of RSV prophylaxis set the stage for other innovative strategies to increase antibody titers as a means of protection against RSV disease [20]. These strategies include both active immunization and passive immunization, with maternal immunization as a strategy to provide protective antibody against RSV to the infant, beginning at birth [21, 22]. Recent breakthroughs in the path toward an effective RSV vaccine include the description of the molecular structure and function of the RSV F protein [23, 24], as well as increased acceptance of maternal immunization as a vaccination platform following the 2009 influenza pandemic and recent pertussis epidemics [25, 26]. The unmet clinical need for RSV infection prevention has become globally recognized by researchers, foundations, and the pharmaceutical industry. These factors have accelerated the development of RSV vaccines at an unparalleled rate, and this is good news. Tracking of new and potential RSV vaccines and monoclonal antibody products by PATH, an international health organization based in Seattle, Washington, has documented the rapid increase in RSV vaccines under development from “less than a handful” in 2004 [27, p 149] to >60 in 2016 [28] (Figure 1). Strategies for these vaccines include passive antibody transfer by maternal immunization of the mother with F-protein vaccines, active immunization of adults and elderly individuals with similar protein vaccines, and active immunization of healthy or at-risk children with live-attenuated vaccines delivered intranasally. The fact that RSV vaccines have the potential for commercial development and widespread clinical use now appears to be well recognized and certainly has the potential to influence the health of children and elderly individuals globally. Received 9 September 2016; accepted 13 September 2016; published online 29 September 2016. Correspondence: J. A. Englund, 4800 Sand Point Way NE, MA7.234, Seattle, WA 98105 (janet.englund@seattle childrens.org). The Journal of Infectious Diseases 2017;215:4–7 © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. DOI: 10.1093/infdis/jiw455