Early efforts to develop RSV vaccines in the 1960s backfired, increasing RSV-related hospitalizations.6 Because there is still no specific treatment or vaccine for RSV, research efforts have emphasized immunoprophylaxis and prevention of transmission, particularly among infants and young children who are at high risk for severe infection.4 Transmission prevention involves cough and sneeze etiquette and hand hygiene, and avoiding the sharing of plates, cups and utensils.4

Immunoprophylaxis with monthly intramuscular injections of the humanized monoclonal antibody palivizumab was approved by the US Food and Drug Administration (FDA) to reduce the risk of serious RSV infections in high-risk children in 1998 and was subsequently recommended for high-risk infants and young children during RSV season by the American Academy of Pediatrics (AAP).8 FDA approval followed findings in the Impact clinical trial, that prophylaxis was associated with a 55% reduction in hospitalizations attributable to RSV infection among high-risk infants.6,9

In July 2014, the AAP updated its 2006 guidelines to better delineate who is at highest risk for serious RSV infection.8 The updated guidance recommend palivizumab prophylaxis for infants born before 29 weeks’ gestation, but not for otherwise healthy infants born after 29 weeks’ gestation. Among children with chronic lung disease of prematurity, palivizumab prophylaxis was recommended during the first year of life for pre-term infants who were born prior to a gestational age of 32 weeks.8 The 2014 AAP guidelines no longer recommends against the use of bronchodilators, continuous pulse oximetry, or high-flow cannula.6,8 The AAP has not recommended inhaled ribavirin for children with severe RSV infection for more than two decades.6

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Investigational Agents

New investigational therapeutics are undergoing clinical development, including antivirals with and continued work on live-attenuated and subunit vaccines for prevention.3,6 Eleven investigational antivirals are in clinical-trial testing for RSV.6

Among promising antivirals are agents that target viral RNA’s role in protein synthesis. For example, the small interfering RNA (siRNA) agent ALN-RSV01 silences messenger RNA encoding a key viral protein (N protein), and the small-molecule inhibitor ALS-008176 inhibits RNA polymerase function and hence protein production.6,10,11 Preclinical research suggests that RSV nucleolin-targeting therapies might also be worth clinical investigation.6

In 2010, the FDA Antiviral Drugs Advisory Committee recommended against approval of motavizumab, another humanized monoclonal antibody, citing lack of superiority to palivizumab.12 However, findings from a subsequently-published phase 3 randomized, double-blind, placebo-controlled trial indicate that motavizumab helps to reduce hospitalization among healthy full-term Native American infants, a population that faces elevated risks for severe RSV infection.12,13 

*This may be true based on reported numbers, but RSV diagnositcs are not available in most developing parts of the world, so the illness doesnt get labeled as such, and with more widespread HIB and pneumococcal vaccines available, RSV is most certainly the leading casue of mortality across the globe

From Our Advisory Board

This is an exciting time to work in the research area of RSV treatment and prevention. New antiviral medications with potent activity are now being tested in clinical trials, with several new prevention strategies being explored.

Imagine a future where pregnant mothers can opt for a vaccination during pregnancy, which boosts their immunity to RSV so that transplacental antibody protects their infant from RSV infection in the first months of life. Envision a monoclonal antibody with an extended plasma half-life that can be administered as a single injection to all newborns discharged during RSV season that could protect them from RSV for the entire first season. Imagine virus-like particle vaccines that can be administered to children at risk, or to those with a newborn sibling on the way rendering them protected from re-infection and exposing their newborn sibling to RSV. Imagine a similar vaccine that can be administered to elderly adults at the same time they receive their influenza vaccine to further reduce respiratory morbidity during cold and flu season. 

Efforts to realize all of these imagined goals are already well on their way, many of them having already passed through phase I and II to enter large scale phase III efficacy trials in the fall of 2016 The future of RSV prevention is finally becoming a reality. RSV disease burden will change in the coming years based on the proof of these efforts. Dramatic reductions in hospitalizations for moderate to severe RSV disease is finally within reach.