Progress toward a Respiratory Syncytial Virus Vaccine

Abstract

Respiratory syncytial virus is the leading cause of serious lower respiratory disease in young children throughout the world. An estimated 3.4 million children younger than 5 years of age are hospitalized each year with severe respiratory syncytial virus (RSV) lower respiratory tract infection, with the highest incidence in children younger than 6 months of age. Up to 200,000 deaths occur annually, with most deaths occurring in children younger than 1 year of age and in developing-country settings (1). Unfortunately, options for prevention and control are limited. No RSV vaccine is licensed anywhere in the world. While prophylactic treatment with RSV-specific neutralizing antibody is effective in reducing RSV morbidity in infants, its use is currently limited to select populations in high-resource settings because of its expense and because of challenges with its delivery (2). Prevention of severe RSV disease through active immunization of infants would be optimal but has been extremely challenging to implement, given the young age by which immunity is necessary and the legacy of vaccine-enhanced illness leading to deaths in a number of young children after receipt of a formalin-inactivated RSV vaccine in the 1960s.In this issue of Clinical and Vaccine Immunology, two articles address important obstacles in the path to a successful RSV vaccine (3, 4). Acosta and colleagues provide a history and perspective on the vaccine-enhanced RSV illness that occurred in the 1960s. The devastating results from those trials have thwarted vaccine efforts for the past 5 decades. The authors summarize the large and important body of work that has informed our understanding of immune responses in seronegative infants. The authors caution that RSV vaccines triggering high levels of interleukin-4 (IL-4) and/or IL-13 are associated with enhanced disease in animal models and should be excluded as potential candidates for infant immunization. Likewise, vaccines eliciting nonneutralizing antibody may also be quite risky in seronegative individuals (3).The second article addresses the important issue of identifying a correlate of protection, which if established could make vaccine licensure easier to achieve. Vissers et al. studied a cohort of infants hospitalized with RSV infection in the Netherlands to determine the importance of serum versus mucosal antibody, presumed to be maternally derived given the young age of the infants (mean, 53 days). The authors found that RSV-specific mucosal IgG concentrations, but not plasma IgG concentrations, inversely correlated with viral load (4). While the results are provocative, the study was limited by its small sample size and cross-sectional design. It will be important to replicate these results in larger populations in other locales. Nonetheless, such innovative work is needed to inform measures of vaccine-induced immunity and accelerate RSV vaccine development.The RSV experience reminds us that vaccine development is by nature a prolonged, risky, and increasingly expensive process. Laborato...

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