Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines

Griffiths, M. E. , Broos, A. , Bergner, L. M. , Meza, D. K., Suarez, N. M., Da Silva Filipe, A. , Tello, C., Becker, D. J. and Streicker, D. G. (2022) Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines. PLoS Biology, 20(4), e3001580. (doi: 10.1371/journal.pbio.3001580) (PMID:35439242) (PMCID:PMC9017877)

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Vaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored “transmissible” vaccines that deliberately spread among hosts are a potentially transformative, but still theoretical, solution to the challenge of immunising inaccessible wildlife. Progress towards real-world application is frustrated by the absence of frameworks to guide vector selection and vaccine deployment prior to major in vitro and in vivo investments in vaccine engineering and testing. Here, we performed deep sequencing on field-collected samples of Desmodus rotundus betaherpesvirus (DrBHV), a candidate vector for a transmissible vaccine targeting vampire bat–transmitted rabies. We discovered 11 strains of DrBHV that varied in prevalence and geographic distribution across Peru. The phylogeographic structure of DrBHV strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies and identifying geographic areas for field trials where vaccine spread would be naturally contained. Multistrain infections were observed in 79% of infected bats. Resampling of marked individuals over 4 years showed within-host persistence kinetics characteristic of latency and reactivation, properties that might boost individual immunity and lead to sporadic vaccine transmission over the lifetime of the host. Further, strain acquisitions by already infected individuals implied that preexisting immunity and strain competition are unlikely to inhibit vaccine spread. Our results support the development of a transmissible vaccine targeting a major source of human and animal rabies in Latin America and show how genomics can enlighten vector selection and deployment strategies for transmissible vaccines.

Item Type:Articles
Additional Information:Funding: M.E.G. was supported by a Medical Research Council scholarship via the MRC-CVR PhD programme (MC_UU_12014/12) (https://mrc.ukri.org/). D.K.M. was supported by the Human Frontier Science Program (RGP0013/2018) (https://www.hfsp.org/) and the Mexican National Council for Science and Technology (CONACYT, 334795/472296) (https://www.conacyt.mx/). A.d.S.F. and N.S. were supported by the Medical Research Council (MC_UU_12014/12; MC_UU_12014/3). D.J.B. was supported by a National Science Foundation Graduate Research Fellowship, (NSF DEB-1601052) (https://www.nsf.gov/), the ARCS Foundation (https://www.arcsfoundation.org/national-homepage), and the Explorer’s Club (https://www.explorers.org/). D.G.S., A.B. and L.M.B. were supported by a Wellcome Trust Senior Research Fellowship (217221/Z/19/Z) (https://wellcome.org/).
Glasgow Author(s) Enlighten ID:Streicker, Professor Daniel and Suarez, Dr Nicolas and Bergner, Dr Laura and Da Silva Filipe, Dr Ana and Broos, Ms Alice and Griffiths, Dr Megan
Creator Roles:
Griffiths, M. E.Conceptualization, Formal analysis, Investigation, Visualization, Writing – original draft
Streicker, D. G.Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review and editing
Broos, A.Data curation, Methodology, Resources
Bergner, L. M.Methodology
Suarez, N. M.Methodology, Software
Da Silva Filipe, A.Resources
Authors: Griffiths, M. E., Broos, A., Bergner, L. M., Meza, D. K., Suarez, N. M., Da Silva Filipe, A., Tello, C., Becker, D. J., and Streicker, D. G.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:PLoS Biology
Publisher:Public Library of Science
ISSN (Online):1545-7885
Published Online:19 April 2022
Copyright Holders:Copyright © 2022 Griffiths et al.
First Published:First published in PLoS Biology 20(4):e3001580
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630014Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)David RobertsonMedical Research Council (MRC)MC_UU_12014/12III - Centre for Virus Research
172630003Persistent Infections (Programme 2)Andrew DavisonMedical Research Council (MRC)MC_UU_12014/3III - Centre for Virus Research
307106Epidemiology meets biotechnology: preventing viral emergence from batsDaniel StreickerWellcome Trust (WELLCOTR)217221/Z/19/ZInstitute of Biodiversity, Animal Health and Comparative Medicine