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Review
. 2020 Jul;125(1):36-46.
doi: 10.1016/j.anai.2020.03.017. Epub 2020 Mar 23.

The journey to a respiratory syncytial virus vaccine

Asuncion Mejias  1 , Rosa Rodríguez-Fernández  2 , Silvia Oliva  3 , Mark E Peeples  4 , Octavio Ramilo  5
Affiliations
Review

The journey to a respiratory syncytial virus vaccine

Asuncion Mejias et al. Ann Allergy Asthma Immunol. 2020 Jul.

Abstract

Objective: The high burden associated with respiratory syncytial virus (RSV) has made the development of RSV vaccine(s) a global health high priority. This review summarizes the journey to an RSV vaccine, the different strategies and challenges associated with the development of preventive strategies for RSV, and the diverse products that are undergoing clinical testing.

Data sources: Studies on RSV biology, immunology, epidemiology, and monoclonal antibodies (mAbs) and vaccines were searched using MEDLINE. We also searched PATH.org and ClinicalTrials.gov for updated information regarding the status of RSV vaccines and mAbs undergoing clinical trials.

Study selections: We selected relevant studies conducted in infants and young children, pregnant women, and elderly population for the prevention of RSV infection.

Results: Identification of a safe and immunogenic vaccine has been an important but elusive initiative for more than 60 years for different reasons, including the legacy of formalin-inactivated vaccine, our limited understanding of the immune response to RSV and how it relates to clinical disease severity, or the need for different end points according to the different vaccine platforms. Nevertheless, there are currently 39 vaccines and mAbs under development and 19 undergoing clinical trials.

Conclusion: Over the past decade, there have been significant advances in our knowledge of RSV molecular and structural biology and in understanding the human immune response to RSV. Despite the barriers, there are several promising mAbs and RSV vaccines undergoing clinical trials that hope to offer protection to the most vulnerable populations.

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Conflict of interest statement

Conflicts of Interest

AM has received fees for participation in advisory boards from Janssen and Roche, and fees for lectures from Abbvie. RR has received fees for participation in advisory boards and lectures from Abbvie. MEP has received fees for participation in an advisory board from ReViral and lectures from Pfizer. OR has received fees for participation in advisory boards from Merck, MedImmune/Sanofi-Pasteur, and Pfizer; and fees for lectures from Pfizer.

Figures

Figure 1.
Figure 1.. The RSV virion.
RSV is an enveloped, negative-sense, single-stranded RNA virus that Its genome contains 10 genes (15,222 nucleotides) that encode eleven proteins. Of the three transmembrane surface glycoproteins, the adhesion (G) and fusion (F) proteins, are crucial for the infectivity and pathogenesis of the virus, and carry the antigenic determinants that elicit the production of neutralizing antibodies by the host. The F glycoprotein is present in the host in two forms, in a metastable prefusion confirmation state (preF) and after the virus fuses with the cell (post-F).
Figure 2.
Figure 2.. Antigenic sites of the RSV F protein and monoclonal antibodies.
The conformation of the Pre-F and post-F proteins and the specific antigenic side are included in the L panel (preF) and R panel (post-F). Of the five major neutralizing sites (Ø, II, III, IV, and V) present on the pre-F surface, site Ø and V are the most neutralization sensitive. Niservimab and suptamuvab are pre-F specific mAb that bind to antigenic site Ø and V respectively, while palivizumab or MK-1654, bind to site-II and IV respectively that are present in the pre-F and post-F conformations. The triangle illustrates from the most to the least neutralization sensitive epitopes.
Figure 3.
Figure 3.. Target populations and RSV vaccine types.
There are different vaccine strategies according to the main target populations. The four main target populations are color coded (red, maternal; infants < 6 months, orange; children >6 months, green; and elderly in blue). The nuances and characteristics of each target population are included in the adjacent balloon and the preferred vaccine strategy underneath each target population.
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