Project

RSV GOLD

Goal: The RSV GOLD project aims to get insight into the risk factors of RSV-related mortality in children under 5 years old and to ultimately reduce the global burden of RSV infection by informing future vaccine development and policy.

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Rsv Gold
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Rsv Gold
added 2 research items
Background: Respiratory syncytial virus (RSV) is a major cause of mortality in children under five years of age worldwide. Down syndrome (DS) is a independent risk factor for severe RSV infection. We aimed to characterize the clinical characteristics of children with DS who died with RSV-confirmed infection in order to predict the impact of maternal vaccination in this group. Conclusion: A significant proportion of children with Down syndrome who died with RSV-confirmed infection have no other comorbidities.
Background Maternal vaccines for RSV are in phase II and III clinical trials. Transplacental RSV antibody transfer is well characterized, but little is known about the postnatal transfer of antibodies via breast milk. Antibodies against the prefusion F (PreF) protein of RSV account for the majority of neutralizing activity in human sera.1 We studied neutralizing antibodies in breast milk. Aim: To investigate the protective effect of antibodies against various epitopes of the RSV F glycoprotein in breast milk against RSV acute respiratory infection. Conclusion: IgG antibodies against the PreF protein of RSV may serve as a correlate of protection against RSV confirmed ARI in the first 6 months of life
Natalie Mazur
added 2 research items
Provisions for post-trial access (PTA) of the experimental intervention are required before the start of a clinical trial. Although there has been ample attention for PTA in the context of preventive vaccine research, discussions on PTA barely include maternal vaccine trials in which mother-infant pairs are exposed to the intervention. In maternal vaccination trials, specific PTA arrangements are required because pregnancy is transient and PTA may apply to the next pregnancy or the child. In this article, we examine the application and adherence to PTA in the context of maternal vaccine trials. We focused on differences between publications before and after 2000 when international ethical guidance documents formalized PTA requirements. Randomized maternal vaccine trials were included after a systematic search for clinical trials in phases II and III with a maternal vaccine as intervention. We used PTA as defined at the time of publication in the World Medical Association's Declaration of Helsinki (DoH) or in the ethical guidelines of the Council for International Organizations of Medical Sciences (CIOMS). In addition, we investigated whether PTA was included in the trial design. Therefore, we contacted principal investigators (PI's) of the publications found in the review to fill out a questionnaire regarding provisions for PTA. Before and after 2000, no trial articles examined in the systematic review described PTA in their trial publication (0/7, 0% and 0/17, 0%, respectively). In addition, more than half of the PI's of the trials found were not familiar with PTA recommendations in international ethical guidelines. Most cases of PTA included making knowledge available by publishing the results of the trial. The revision of the DoH in 2002 and the CIOMS ethical guidelines in 2002 has not resulted in increased PTA provisions for maternal vaccination trials. PTA is a shared responsibility of various stakeholders including sponsors, Institutional Review Boards, regulators, political entities, and researchers. Inclusion of PTA provisions in trial protocols and publications on maternal vaccination trials is essential to increase transparency on the form and content of these provisions.
Rsv Gold
added 5 research items
Background: Transplacental RSV antibody transfer has been characterized, but little is known about the protective effect of breast milk RSV-specific antibodies. Serum antibodies against the prefusion RSV fusion protein (pre-F) exhibit high neutralizing activity. We investigate protection of breast milk pre-F antibodies against RSV acute respiratory infection (ARI). Methods: Breast milk at 1, 3, and 6 months postpartum and mid-nasal swabs during infant illness episodes were collected in mother-infant pairs in Nepal. 174 infants with and without RSV ARI were matched 1:1 by risk factors for RSV ARI. Pre-F IgA and IgG antibody levels were measured in breast milk. Results: The median breast milk pre-F IgG antibody concentration before illness was lower in mothers of infants with RSV ARI (1.4, IQR 1.1-1.6 log10 ng/mL) than without RSV ARI (1.5, IQR: 1.3-1.8 log10 ng/mL, p=0.001). There was no difference in median maternal pre-F IgA antibody concentrations in cases (1.7, IQR: 0.0-2.2 log10 ng/mL) versus controls (1.7, IQR: 1.2-2.2 log10 ng/mL, p=0.58). Conclusion: Low breast milk pre-F IgG antibodies before RSV ARI supports a potential role for pre-F IgG as a correlate of protection against RSV ARI. Induction of breast milk pre-F IgG may be a mechanism of protection for maternal RSV vaccines.
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.
Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. Findings We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 months (2·0–10·0) in upper middle-income countries, and 7·0 months (3·6–16·8) in high-income countries. Interpretation This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries. Funding Bill & Melinda Gates Foundation.
Rsv Gold
added a project goal
The RSV GOLD project aims to get insight into the risk factors of RSV-related mortality in children under 5 years old and to ultimately reduce the global burden of RSV infection by informing future vaccine development and policy.
 
Rsv Gold
added 2 research items
Background: Respiratory syncytial virus (RSV) infection is an important cause of infant mortality. Here, we estimated the potential impact of maternal vaccination against RSV on life-threatening RSV infection in infants. Methods: We developed a mathematical model for maternal vaccine-induced antibody dynamics and used characteristics of a maternal RSV vaccine currently in phase 3 of clinical development. The model was applied to data from two cohorts of children younger than 12 months with RSV-related paediatric intensive care unit (PICU) admission in the United Kingdom (n = 370) and the Netherlands (n = 167), and a cohort of 211 children younger than 12 months with RSV-related in-hospital death from 20 countries worldwide. Results: Our model predicted that, depending on vaccine efficiency, maternal vaccination at 30 weeks' gestational age could have prevented 62-75% of RSV-related PICU admissions in the United Kingdom and 76-87% in the Netherlands. For the global mortality cohort, the model predicted that maternal vaccination could have prevented 29-48% of RSV-related in-hospital deaths. Preterm children and children with comorbidities were predicted to benefit less than (healthy) term children. Conclusions: Maternal vaccination against RSV may substantially decrease life-threatening RSV infections in infants.
BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. METHODS: In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms "RSV", "respiratory syncytial virus", or "respiratory syncytial viral" combined with "mortality", "fatality", "death", "died", "deaths", or "CFR" for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. FINDINGS: We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3-11·0) in low-income or lower middle-income countries, 4·0 years (2·0-10·0) in upper middle-income countries, and 7·0 years (3·6-16·8) in high-income countries. INTERPRETATION: This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries.