Benefit and harm from immunity to respiratory syncytial virus: implications for treatment

Human respiratory syncytial virus (RSV) infection is a major cause of morbidity in children and of morbidity and mortality in elderly or immunocompromised adults. Given prophylactically, antibody can protect against infection, but natural levels are poorly protective. Vaccination may enhance disease, and there is no well tolerated and effective vaccine or antiviral treatment. Despite over 50 years of research, therapy remains nonspecific and supportive.

Experimental human challenge in adult volunteers is beginning to elucidate the dynamics of viral shedding and causes of disease, but investigations of naturally infected children remain logistically challenging. RSV was known to bind several surface ligands, but the recent demonstration that nucleolin acts as a receptor for the RSV fusion protein was unexpected. Recent studies increasingly emphasize the relevance of innate immune responses and the dysregulation of inflammation as key factors in causing the pathological effects of infection. Studies in both human infants and mice indicate that interleukin-17 plays a role in some forms of RSV disease and regulatory T cells may be important in controlling inflammation.

Improved understanding of the human immune response to RSV infection continues to be needed in order to accelerate the development of vaccines and new treatments for bronchiolitis.