The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates.
Mazur NI, Higgins D, Nunes MC, Melero JA, Langedijk AC, Horsley N, Buchholz UJ, Openshaw PJ, Mc Lellan JS, Englund JA, Meijas A, KArron RA, Simōes EA, Knezevic I, Ramilo O, Piedra PA, Chu HY, Falsey AR, Nair H, Kragten-Tabatabaie L, Greenough A, Baraldi E, Papadopoulus NG, Vekenmans J, Polack FP, Powell M, Satav A, Walsh EE, Stein RT, Graham BS, Bont LJ, Respiratory Syncytial Virus Network (ReSViNET) Foundation.
The global burden of disease caused by respiratory syncytial virus (RSV) is increasingly recognised, not only in infants, but also in older adults (aged ≥65 years). Advances in knowledge of the structural biology of the RSV surface fusion glycoprotein have revolutionised RSV vaccine development by providing a new target for preventive interventions. The RSV vaccine landscape has rapidly expanded to include 19 vaccine candidates and monoclonal antibodies (mAbs) in clinical trials, reflecting the urgency of reducing this global health problem and hence the prioritisation of RSV vaccine development. The candidates include mAbs and vaccines using four approaches: (1) particle-based, (2) live-attenuated or chimeric, (3) subunit, (4) vector-based. Late-phase RSV vaccine trial failures highlight gaps in knowledge regarding immunological protection and provide lessons for future development. In this Review, we highlight promising new approaches for RSV vaccine design and provide a comprehensive overview of RSV vaccine candidates and mAbs in clinical development to prevent one of the most common and severe infectious diseases in young children and older adults worldwide.
Obando-Pacheco P, Justicia-Grande AJ, Rivero-Calle I, Rodríguez-Tenreiro C, Sly P, Ramilo O, Mejías A, Baraldi E, Papadopoulos NG, Nair H, Nunes MC, Kragten-Tabatabaie L, Heikkinen T, Greenough A, Stein RT, Mazoni P, Bont L, Martinón-Torres F.
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children. By the age of 1 year, 60%-70% of children have been infected by RSV. In addition, early-life RSV infection is associated with the development of recurrent wheezing and asthma in infancy and childhood. The need for precise epidemiologic data regarding RSV as a worldwide pathogen has been growing steadily as novel RSV therapeutics are reaching the final stages of development. To optimize the prevention, diagnosis, and treatment of RSV infection in a timely manner, knowledge about the differences in the timing of the RSV epidemics worldwide is needed. Previous analyses, based on literature reviews of individual reports obtained from medical databases, have failed to provide global country seasonality patterns. Until recently, only certain countries have been recording RSV incidence through their own surveillance systems. This analysis was based on national RSV surveillance reports and medical databases from 27 countries worldwide. This is the first study to use original-source, high-quality surveillance data to establish a global, robust, and homogeneous report on global country-specific RSV seasonality.
The burden of respiratory syncytial virus (RSV) associated acute lower respiratory infections in children with Down syndrome: A systematic review and meta-analysis.
Chan M, Park JJ, Shi T, Martinón-Torres F, Bont L, Nair H, Respiratory Syncytial Virus Network (ReSViNET).
Acute lower respiratory tract infections (ALRIs) caused by respiratory syncytial virus (RSV) are a leading cause of hospitalization in infants. Numerous risk factors have been identified in the aetiology of severe RSV-associated ALRI necessitating hospitalisation, including prematurity and congenital heart disease. Down syndrome (DS), a common genetic disorder associated with congenital and dysmorphic features, has recently been identified as an independent risk factor for RSV-associated ALRI requiring hospitalisation; however, the disease burden of RSV-associated ALRI in this population has not yet been established. Similarly, the impact of DS as an independent risk factor has not yet been quantified. We aimed therefore to estimate the incidence of admissions in children with DS, and by comparing this with unaffected children, to quantify the risk of DS independent of other risk factors.
We are very proud to announce that our board member, Dr. Federico Martinón Torres and his team, designed a new clinical scale for infants with acute respiratory infection, the ReSVinet scale. Our scale is based on seven parameters (feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition, fever) that were assigned different values (from 0 to 3) for a total of 20 points. 170 children under two years of age with ARI were assessed independently by three pediatricians using this scale.
We invite you to read the full report by downloading the file via the link below
We are delighted to inform you that the report of our successful ReSViNET meeting in Zeist (2-3 March 2016) is published in “Journal of Global Health”. We invite you to read the full report by downloading the file via the link below.
Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics
Mazur NI,Martinón-Torres F, Baraldi E, Fauroux B, Greenough A, Heikkinen T, Manzoni P, Mejias A, Nair H, Papadopoulos NG, Polack FP, Ramilo O, Sharland M, Stein R, Madhi SA, Bont L, in collaboration with Respiratory Syncytial Virus Network (ReSViNET)
Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and oxygenation, remains the cornerstone of clinical management. However, RSV treatments in development in the past decade include 10 vaccines and 11 therapeutic agents in active clinical trials. Maternal vaccination is particularly relevant because the most severe disease occurs within the first 6 months of life, when children are unlikely to benefit from active immunisation. We must optimise the implementation of novel RSV therapeutics by understanding the target populations, showing safety, and striving for acceptable pricing in the context of this worldwide health problem. In this Review, we outline the limitations of RSV LRTI management, the drugs in development, and the remaining challenges related to study design, regulatory approval, and implementation.
Bont L, MD, Baraldi E, Fauroux B, Greenough A, Heikkinen T, Manzoni P, Martinón-Torres F, Nair H, Papadopoulos NG, on behalf of ReSViNET.
THE NEED FOR RSC RESEARCH NETWORKS
Key research questions can seldom be answered without multidisciplinary and networking approaches. For influenza such approaches have been developed (GABRIEL, isirv, MISMS and CEIRS). The BRaVe initia- tive by World Health Association is an action plan to decrease the unmet global burden of respiratory viruses in general. TB-net is a net- work to promote clinically oriented research in the field of tuberculosis in Europe by shar- ing and developing ideas and research pro- tocols. Despite the major burden of disease, there is no international, integrated, multidis- ciplinary and translational research approach focused on RSV infections. National RSV networks, such as the Italian Neonatology Study Group on RSV Infections and the Dutch RSV Neonatal Network do not have the multidisciplinary potential to address most major scientific challenges. At the same time, research interest in RSV keeps growing, with an increasing number of studies underway and more to appear with the development of new preventive and therapeutic molecules. Most trials are currently being performed in the United States and Europe, with twice as much studies in the United States as in Europe (Fig. 1). In this setting, ReSViNET is a new fully independent research network with the mission to decrease the global bur- den of RSV infection by integrating exper- tise. It addresses the burden of RSV by estab- lishing a European translational research framework and by delivering a comprehen- sive training and education program. ReSVi- NET is stimulating and performing research aiming to understand and tackle the burden of RSV infection, to advocate for better care for patients with RSV infection, to provide education related to RSV infection and to provide effective partnerships with relevant stakeholders. Although founded by European researchers, the network open to researchers outside of Europe, such as investigators from developing countries through RSV GEN led by University of Edinburgh. Combining expertise will eventually enable streamlining research efforts to decrease the global burden of RSV infection.