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Review
. 2022 May;32(3):e2284.
doi: 10.1002/rmv.2284. Epub 2021 Sep 20.

A systematic review on global RSV genetic data: Identification of knowledge gaps

Annefleur C Langedijk  1 , Eline R Harding  1 , Burak Konya  1 , Bram Vrancken  2 , Robert Jan Lebbink  3 , Anouk Evers  3 , Joukje Willemsen  1 , Philippe Lemey  2 , Louis J Bont  1   4
Affiliations
Review

A systematic review on global RSV genetic data: Identification of knowledge gaps

Annefleur C Langedijk et al. Rev Med Virol. 2022 May.

Abstract

Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking resistance against therapeutics currently under development. Since 2015, the field of RSV molecular epidemiology has evolved rapidly with around 20-30 published articles per year. The objective of this systematic review is to identify knowledge gaps in recent RSV genetic literature to guide global molecular epidemiology research. We included 78 studies published between 2015 and 2020 describing 12,998 RSV sequences of which 8,233 (63%) have been uploaded to GenBank. Seventeen (22%) studies were performed in low- and middle-income countries (LMICs), and seven (9%) studies sequenced whole-genomes. Although most reported polymorphisms for monoclonal antibodies in clinical development (nirsevimab, MK-1654) have not been tested for resistance in neutralisation essays, known resistance was detected at low levels for the nirsevimab and palivizumab binding site. High resistance was found for the suptavumab binding site. We present the first literature review of an enormous amount of RSV genetic data. The need for global monitoring of RSV molecular epidemiology becomes increasingly important in evaluating the effectiveness of monoclonal antibody candidates as they reach their final stages of clinical development. We have identified the following three knowledge gaps: whole-genome data to study global RSV evolution, data from LMICs and data from global surveillance programs.

Keywords: RSV; molecular epidemiology; monoclonal antibodies; respiratory syncytial virus; systematic review.

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Conflict of interest statement

Annefleur C. Langedijk, Eline R. Harding, Burak Konya, Bram Vrancken, Robert Jan Lebbink, Anouk Evers, Joukje Willemsen and Philippe Lemey do not report conflicts of interest. Louis J. Bont has not received personal fees or other personal benefits. UMCU has received funding from Abbvie, AstraZeneca, Janssen, the Bill and Melinda Gates Foundation, Nutricia (Danone) and MeMed Diagnostics. UMCU has received major cash or in kind funding as part of the public private partnership IMI‐funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. UMCU has received major funding by Julius Clinical for participating in the INFORM study sponsored by AstraZeneca. UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015 to 2017. UMCU received minor funding for consultation and invited lectures by AbbVie, AstraZeneca, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, Janssen. LJB is the founding chairman of the ReSViNET Foundation. Nirsevimab development is jointly funded by AstraZeneca and Sanofi Pasteur.

Figures

FIGURE 1
FIGURE 1
Study selection
FIGURE 2
FIGURE 2
Continental distribution of sequences (n = 6 continents)
FIGURE 3
FIGURE 3
Amino acid polymorphisms detected at ≥10% frequency (Table S4) are highlighted with arrows. Previously defined mAb binding sites are delineated in colour (green = nirsevimab, orange = palivuzumab, blue = suptavumab, yellow = MK‐1654). A and B superscripts denote subtype A and B, respectively
FIGURE 4
FIGURE 4
Geographic distribution of all sequences (n = 43 countries)
FIGURE 5
FIGURE 5
Temporal distribution of recent sequences. The bars show the time period of sample collection. Countries included in this review are shown on the y‐axis. The time line from 2010–2020 is shown on the x‐axis. The continents are coloured according to the legend
FIGURE 6
FIGURE 6
Reported RSV A and RSV B genotype distribution (2015–2020). RSV, respiratory syncytial virus
See this image and copyright information in PMC

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