Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is a single, negative-sense mRNA virus (Baltimore classification Group V) belonging to the Pneumoviridae family, and is the most common cause of hospitalizations for lower respiratory tract infections in infants. Although RSV reinfection results in mild to moderate cold-like symptoms among older children and adults, RSV infection poses an elevated risk of pneumonia, acute exacerbation of underlying issues, or death for immunocompromised and elderly patients [1], and has been associated with elevated long-term risk for developing asthma and allergies in young children after severe RSV infection [2][3].

No licensed vaccine exists for RSV to date, although the monoclonal antibody prophylactic treatment, palivizumab (brand name Synagis) is available for premature or newborn infants at a high cost and limited availability. Attempts to develop an RSV vaccine are not new – the first RSV vaccine clinical trial began in the 1960s using a formalin-inactivated RSV. Formalin inactivation destabilizes the surface fusion (F) protein responsible for viral cell entry, so that F protein epitopes critical for RSV neutralization were not present during inoculation and affinity maturation was directed towards non-protective antibody production [4]. This resulted in vaccine-associated enhanced respiratory disease, or in other words, the young children who were seronegative (not previously exposed) that received the formalin-inactivated virus developed severe respiratory illnesses upon natural infection as opposed to their seropositive cohorts.

[1]Coultas JA, Smyth R, Openshaw PJ (October 2019). Respiratory syncytial virus (RSV): a scourge from infancy to old age. Thorax. 74 (10): 986–993.
[2]Jartti T, Gern JE (October 2017). Role of viral infections in the development and exacerbation of asthma in children. The Journal of Allergy and Clinical Immunology. 140 (4): 895–906.
[3]Castro-Rodriguez JA, Forno E, Rodriguez-Martinez CE, Celedón JC (2016). Risk and Protective Factors for Childhood Asthma: What Is the Evidence? . The Journal of Allergy and Clinical Immunology. 4 (6): 1111–1122.
[4]Killikelly, A., Kanekiyo, M. & Graham, B. (2016) Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus. Sci Rep 6, 34108.