Development of respiratory syncytial virus (RSV) vaccines for infants.

2017 will mark the 60th anniversary since the first isolation of RSV in children. In spite of concerted efforts over all these years, the goal of developing an effective vaccine against paediatric RSV disease has remained elusive. One of the main hurdles standing in the way of an effective vaccine is the fact that the age incidence of severe disease peaks within the first 3 months of life, providing limited opportunity for intervention. In addition to this complexity, the spectre of failed historical vaccines, which increased the risk of illness and death upon subsequent natural infection, has substantially increased the safety criteria against which modern vaccines will be assessed. This review traces the history of RSV vaccine development for young infants and analyses the potential reasons for the failure of historic vaccines. It also discusses recent breakthroughs in vaccine antigen design and the progressive evolution of platforms for the delivery of these antigens to seronegative infants.

Prevention of serious respiratory syncytial virus-related illness. I: Disease pathogenesis and early attempts at prevention.

Respiratory syncytial virus (RSV) was first described 160 years ago but was not officially recognized as a cause of serious illness in children until the late 1950s. It has been estimated that virtually all children have had at least one RSV infection by their second birthday. RSV is responsible for annual disease outbreaks, usually during a defined winter seasonal period that can vary by community and year. RSV is recognized as the leading cause of hospitalization among young children worldwide. Infants of young chronologic age and children with predisposing factors, such as premature birth, pulmonary disease, or congenital heart disease, are most susceptible to serious illness. Unlike other viruses, immunity to RSV infection is incomplete and short lived, and reinfection is common throughout life. Initial attempts to develop a vaccine in the 1960s met with unexpected and tragic results; many children vaccinated with a formalin-inactivated wild-type virus developed serious pulmonary disease upon subsequent natural infection. Numerous other vaccine technologies have since been studied, including vectored approaches, virus-like particles, DNA vaccines, and live attenuated virus vaccine. As of early 2010, only two companies or institutions had RSV vaccine candidates in early clinical trials, and no vaccine is likely to be licensed for marketing in the immediate future.

Involvement of antibody, complement and cellular immunity in the pathogenesis of enhanced respiratory syncytial virus disease.

In 1966, infants and children in the USA were immunized with a formalin-inactivated vaccine against respiratory syncytial virus. The vaccine was immunogenic but elicited mainly nonprotective antibody. Upon exposure to respiratory syncytial virus in the community, immunized children developed severe pulmonary disease characterized by bronchoconstriction and pneumonia. Two immunized infants died as toddlers after respiratory syncytial virus infection. Exploration of the mechanisms of disease has dominated the literature for decades. In this review, the pathogenesis of enhanced respiratory disease is discussed and the characteristics of protective and pathogenic respiratory syncytial virus vaccines are examined.