MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

DIVERGE (DIVErsity in Rsv GEnomes)

A multinational collaboration that aims to improve our understanding of RSV disease.

Diverge logo

In 2015, work led by researchers at University of Edinburgh estimated that infection with Respiratory Syncytial Virus (RSV) resulted in 33.1 million episodes of lower respiratory infection (bronchiolitis and pneumonia), leading to 3.2 million hospitalizations and 120,000 deaths worldwide in children younger than five years [1]. The majority of these deaths occur in Low and Middle Income Countries (LMICs), where access to hospital facilities is limited. Little data exists on RSV genomic variability in LMICs, limiting our understanding of the worldwide transmission dynamics of the virus, and how new strains emerge and compete with one another. Several RSV vaccine candidates using a variety of approaches (from maternal immunization to live attenuated vaccines) are in clinical development, and it is likely that one or more of these vaccines will be available in the next five years. A better understanding of viral genomic variability will assist stakeholders in making decisions regarding the introduction of these vaccines into national programmes. 

We have published a paper that looked at genetic variability in the RSV F protein - the protein most likely to be targeted by immunisation campaigns- and found a considerable degree of variability in the limited number of strains available in public databases. Variability was concentrated in particular epitopes (antibody binding regions), which has implications for the type of immunisation campaign that is most likely to be effective.

Given the limited RSV genomic data available, DIVERGE (DIVErsity in Rsv GEnomes) is a multinational collaboration that aims to improve our understanding of RSV disease. It brings together researchers working in LMICs with the National Institute for Allergy and Infectious Diseases, the J.Craig Venter Institute, the Fogarty International Center (all in the United States),  and the University of Edinburgh. We will be carrying out whole genome sequencing of over eight hundred RSV samples taken from children under five years of age. These samples will come from six LMICs located in five of the World Health Organisation regions, extending the global coverage of our knowledge of RSV variability from its current limited base. With samples dating from 2010 to 2017, we aim to achieve a better understanding of RSV transmission dynamics, and relate genetic variability in the virus to clinical presentation. By carrying out deep sequencing of the samples, we will examine whether host-pathogen interactions may be driving within host genetic variability, which if the case, will have implications for decisions on which immunisation strategies are likely to be most effective.

Diverge Partners Map

Diverge Partners Map
Diverge workshop participants
Attendees from left to right: Harry Campbell, Harish Nair, Kate Templeton, Thomas Williams, Elizabeth Wastnedge, Marcela Echavarria, Rachel Reeves, Sandra Jackson, Erik Karlsson, Gene Tan, Andrew Rambaut.

Countries with complete RSV genomes available

 

On the 28th and 29th of June partners in the DIVERGE consortium participated in a workshop in Edinburgh facilitated by the UK Government's Global Challenges Research Fund. The meeting report is now available.

 

People

Professor Quique Bassat Lead investigator for Morocco and Mozambique
Professor Fernando Polack Lead investigator for Argentina
Professor Aubree Gordon Lead investigator for Nicaragua
Professor Abdullah Brooks Lead investigator for Bangladesh
Dr. Erik Karlsson Lead investigator for Cambodia
Dr. Thomas Williams Principal Investigator
Professor Gene Tan Lead for sequencing
Professor David Spiro Co-investigator
Professor Martha Nelson Co-investigator
Professor Harry Campbell Co-investigator
Professor Harish Nair Co-investigator
Professor Kate Templeton Co-investigator

RSV vaccines in development

 

Site Investigators

Name: Professor Quique Bassat

Role: Lead investigator for Morocco and Mozambique

Research Institute: ISGlobal Barcelona Institute for Global Health, Spain

ISGLOBAL Barcelona Institute for Global Health

 

Name: Professor Fernando Polack

Role: Lead investigator for Argentina

Research Institute: Fundacion INFANT, Argentina

 

Name: Professor Aubree Gordon

Role: Lead investigator for Nicaragua

Research Institute: School of Public Health University of Michigan, USA

 

Name: Professor Abdullah Brooks

Role: Lead investigator for Bangladesh

Research Institute: Center for Global Health Johns Hopkins University, USA

 

Name: Dr. Erik Karlsson

Role: Lead investigator for Cambodia

Research Institute: Virology Unit Institut Pasteur, Cambodia

Institut Pasteur du Cambodge

 

Name: Dr. Thomas Williams

Role: Principal Investigator

Research Institute: IGMM, University of Edinburgh, UK

Taylor Lab Evolutionary Genetics and Genomics

 

Name: Professor Gene Tan

Role: Lead for sequencing

Research Institute: Infectious Disease Group, J. Craig Venter Institute, USA

 

Name: Professor David Spiro

Role: Co-investigator

Research Institute: Fogarty International Center, National Institutes of Health, USA

 

Name: Professor Martha Nelson

Role: Co-investigator

Research Institute: Fogarty International Center, National Institutes of Health, USA

 

Name: Professor Harry Campbell

Role: Co-investigator

Research Institute: Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK

Harry Campbell - Professor of Genetic Epidemiology and Public Health

 

Name: Professor Harish Nair

Role: Co-investigator

Research Institute: Usher Institute of Population Health Sciences and Informatics

Harish Nair - Professor of Paediatric Infectious Diseases and Global Health

 

Name: Professor Kate Templeton

Role: Co-investigator

Research Institute: Division of Infection and Pathway Medicine, Edinburgh Medical School, UK

Dr Kate Templeton - Consultant Clinical Scientist, RIE and Honorary Senior Lecturer in Medical Microbiology

 

RESCEU – REspiratory Syncytial virus Consortium in EUrope

 

Key Publications

Shi, T. et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet (2017). doi:10.1016/S0140-6736(17)30938-8

Mas V, Nair H, Campbell H, Melero JA, Williams TC. Antigenic and sequence variability of the human respiratory syncytial virus F glycoprotein compared to related viruses in a comprehensive dataset. Vaccine (2018).  doi:10.1016/J.VACCINE.2018.09.056.

 

Grants

£3 815 EGR&PF – 171809 (UK Government Global Challenges Research Fund).