Abstract
Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent. In the last 50 years, conceptually different approaches failed to evolve into viable preventive alternatives for routine use. Inactivated RSV vaccine (that is, formalin-inactivated RSV) elicited severe LRTI in RSV-infected toddlers pre-immunized as infants; early purified F protein approaches in pregnant women failed to elicit sufficient immunity more than a decade ago; a second-generation monoclonal antibody (mAb) of high potency against the virus (that is, motavizumab) caused severe adverse reactions in the skin, and owing to lack of efficacy against RSV subgroup B, an extended half-life mAb targeting site V in the RSV fusion protein (that is, REG2222) did not meet its primary endpoint. In the meantime, two protein F vaccines failed to prevent medically attended LRTI in the elderly. However, palivizumab and the recent results of the Novavax maternal immunization trial with ResVax demonstrate that severe RSV LRTI can be prevented by mAb and by maternal immunization (at least to a certain extent). In fact, disease prevention may also decrease the rates of recurrent wheezing and all-cause pneumonia for at least 180 days. In this review, we discuss the history of RSV vaccine development, previous and current vaccine strategies undergoing evaluation, and recent information about disease burden and its implications for the effects of successful preventive strategies.
Highlights
Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent
In 1962, following the isolation of the chimpanzee coryza agent—later renamed respiratory syncytial virus (RSV)—by Robert Chanock, the first vaccine against RSV was evaluated in 54 children in the US
Two immune correlates are accepted as the main determinants of enhancement: the presence of low-avidity, non-protective antibodies elicited by immunization[5,6,7] and a polarization of the immune response toward T helper 2 (Th2) in the respiratory tract after RSV infection[8,9]
Summary
F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. Adults older than 65 years may experience disease rates comparable to those elicited by influenza virus and are targeted for protection using active immunization with different constructs Preventive strategies for the latter group are beyond the scope of this review, but it is important to note that two consecutive trials by Novavax and MedImmune failed to confer protection against medically attended RSV LRTI in the elderly with primary endpoint efficacies of −7.9% (95% confidence interval [CI] −84 to 37%) and −7.1% (95% CI −106.9 to 44.3%), respectively[46,47,48]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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