1. Medicine
  2. Epidemiology and Global Health
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Reducing RSV hospitalisation in a lower-income country by vaccinating mothers-to-be and their households

  1. Samuel PC Brand  Is a corresponding author
  2. Patrick Munywoki
  3. David Walumbe
  4. Matthew J Keeling
  5. David James Nokes
  1. University of Warwick, United Kingdom
  2. KEMRI-Wellcome Trust Research Centre, Kenya
Research Article
  • Cited 6
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Cite this article as: eLife 2020;9:e47003 doi: 10.7554/eLife.47003

Abstract

Respiratory syncytial virus is the leading cause of lower respiratory tract infection among infants. RSV is a priority for vaccine development. In this study, we investigate the potential effectiveness of a two-vaccine strategy aimed at mothers-to-be, thereby boosting maternally acquired antibodies of infants, and their household cohabitants, further cocooning infants against infection. We use a dynamic RSV transmission model which captures transmission both within households and communities, adapted to the changing demographics and RSV seasonality of a low-income country. Model parameters were inferred from past RSV hospitalisations, and forecasts made over a 10-year horizon. We find that a 50% reduction in RSV hospitalisations is possible if the maternal vaccine effectiveness can achieve 75 days of additional protection for newborns combined with a 75% coverage of their birth household co-inhabitants (∼7.5% population coverage).

Data availability

All data generated or analysed during this study are included in the manuscript, supporting files or on the cited Github Repository. Source data files have been provided for Figures 2-6.

Article and author information

Author details

  1. Samuel PC Brand

    The Zeeman Institute (SBIDER), School of Life Sciences, University of Warwick, Coventry, United Kingdom
    For correspondence
    S.Brand@warwick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0645-5367
  2. Patrick Munywoki

    Virus Epidemiology and Control Group, KEMRI-Wellcome Trust Research Centre, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9419-7155
  3. David Walumbe

    Virus Epidemiology and Control Group, KEMRI-Wellcome Trust Research Centre, Kilifi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  4. Matthew J Keeling

    The Zeeman Institute (SBIDER), School of Life Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. David James Nokes

    The Zeeman Institute (SBIDER), School of Life Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5426-1984

Funding

The Wellcome Trust (102975)

  • David James Nokes

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: March 19, 2019
  2. Accepted: March 26, 2020
  3. Accepted Manuscript published: March 27, 2020 (version 1)
  4. Version of Record published: September 10, 2020 (version 2)

Copyright

© 2020, Brand et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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    Background:

    Excessive plasma histamine concentrations cause symptoms in mast cell activation syndrome, mastocytosis, or anaphylaxis. Anti-histamines are often insufficiently efficacious. Human diamine oxidase (hDAO) can rapidly degrade histamine and therefore represents a promising new treatment strategy for conditions with pathological histamine concentrations.

    Methods:

    Positively charged amino acids of the heparin-binding motif of hDAO were replaced with polar serine or threonine residues. Binding to heparin and heparan sulfate, cellular internalization and clearance in rodents were examined.

    Results:

    Recombinant hDAO is rapidly cleared from the circulation in rats and mice. After mutation of the heparin-binding motif, binding to heparin and heparan sulfate was strongly reduced. The double mutant rhDAO-R568S/R571T showed minimal cellular uptake. The short α-distribution half-life of the wildtype protein was eliminated, and the clearance was significantly reduced in rodents.

    Conclusions:

    The successful decrease in plasma clearance of rhDAO by mutations of the heparin-binding motif with unchanged histamine-degrading activity represents the first step towards the development of rhDAO as a first-in-class biopharmaceutical to effectively treat diseases characterized by excessive histamine concentrations in plasma and tissues.

    Funding:

    Austrian Science Fund (FWF) Hertha Firnberg program grant T1135 (EG); Sigrid Juselius Foundation, Medicinska Understödsförening Liv och Hälsa rft (TAS and SeV).

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