Search

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infection and is responsible for a large proportion of infant morbidity and mortality worldwide. Most RSV-related deaths occur in children under six months, and the majority of these occur in low-income settings. To date, there is no known efficacious treatment for RSV infection; hence, prevention remains an important strategy to reduce the global burden of disease. Monoclonal antibodies and vaccinations are currently the two main approaches for prevention of RSV disease. Maternal RSV vaccination is of particular interest as a strategy to protect infants during their most vulnerable period as this approach has proven highly efficacious in other vaccine-preventable conditions such as pertussis and influenza. As results from ongoing phase III clinical trials become available, important decisions will need to be made about the priority and potential implementation of RSV vaccines alongside other public health measures.

On Jan. 10, Chinese scientists uploaded the genetic sequence of a , later named SARS-CoV-2, to an open-access website, GenBank. The virus had been linked to a growing number of mysterious pneumonia...

Highlights • First study examining potential impact of a maternal RSV vaccine across LMICs. • Results from independent models to inform Gavi’s 2018 Vaccine Investment Strategy. • Experts and stakeholders advised on methods, assumptions, and key model inputs. • Substantial potential to reduce infant morbidity and mortality in Gavi countries., Background Interventions to protect young infants against respiratory syncytial virus (RSV) are in advanced phases of development and are expected to be available in the foreseeable future. Gavi, the Vaccine Alliance, included maternal vaccines and infant monoclonal antibodies for RSV as part of the 2018 vaccine investment strategy (VIS) and decided to support these products subject to licensure, World Health Organization prequalification, Strategic Advisory Group of Experts recommendation, and meeting the financial assumptions used as the basis of the investment case. Impact estimates reported in this manuscript were used to inform the Gavi VIS. Methods We compared two independent vaccine impact models to evaluate a potential maternal RSV vaccine’s impact on infant health in 73 Gavi-supported countries. Key inputs were harmonized across both models. We analyzed various scenarios to evaluate the effect of uncertain model parameters such as vaccine efficacy, duration of infant protection, and infant disease burden. Estimates of averted cases, severe cases, hospitalizations, deaths, and disability-adjusted life years (DALYs) were calculated over the 2023–2035 horizon. Findings A maternal RSV vaccine with 60% efficacy offering 5 months of infant protection implemented across 73 low- and middle-income countries could avert 10.1–12.5 million cases, 2.8–4.0 million hospitalizations, 123.7–177.7 thousand deaths, and 8.5–11.9 million DALYs among infants under 6 months of age for the duration of analysis (2023–2035). Maternal RSV vaccination was projected to avert up to 42% of estimated RSV deaths among infants under 6 months in year 2035. Alternative scenario analyses with higher disease burden assumptions showed that a maternal vaccine could avert as many as 325–355 thousand deaths among infants under 6 months. Interpretation RSV maternal immunization is projected to substantially reduce mortality and morbidity among young infants if introduced across Gavi-supported countries. Funding This work was supported by Bill & Melinda Gates Foundation, Seattle, WA, and Respiratory Syncytial Virus Consortium in Europe. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation or of the Respiratory Syncytial Virus Consortium. LW is supported by Research Foundation–Flanders (1234620 N).

Introduction: Human respiratory syncytial virus (RSV) is a major health threat both for the very young and the elderly. With yearly 3.2 million hospital admissions and approximately 118,000 deaths due to RSV in children across the globe, the impact of this infectious disease is very high. Development of a safe RSV vaccine is of utmost importance but has proven to be challenging for several reasons. Researchers are faced with the history of a failed RSV vaccine trial, difficult target populations, a virus that naturally does not induce a long-lasting immune response and ambiguity concerning the optimal correlate of protection. Many different vaccine formats are being tested in preclinical models and about 30 candidate RSV vaccines are being evaluated in clinical trials.Areas covered: In this review we focus on the difficulties concerning the development of an effective RSV vaccine and discuss vaccines that are currently in clinical trials and how they have dealt with these challenges. We review live-attenuated vaccines, vectored vaccines, subunit vaccines and particle-based vaccines.Expert opinion: It is clear that this field is progressing rapidly with several promising RSV vaccine candidates. A safe and effective RSV vaccine might be on the brink of clinical implementation soon.

Over the past decade, there have been significant advances in our knowledge of RSV molecular and structural biology and in the understanding of the human immune response to RSV. Despite the barriers, there are several opportunities for RSV vaccine development to protect the most vulnerable populations. The increasing interest of academic, industry and international bodies, such as the World Health Organization or Bill & Melinda Gates Foundation, is helping to move the field forward, promoting the implementation of surveillance platforms and standardization of clinical definitions, assays and surrogate markers of protection.

Introduction: Respiratory syncytial virus (RSV) causes high morbidity and mortality rates among infants, young children, and the elderly worldwide. Unfortunately, a safe and effective vaccine is still unavailable. In 1966, a formalin-inactivated RSV vaccine failed and resulted in the death of two young children. This failure shifted research toward the development of subunit-based vaccines for pregnant women (to passively vaccinate infants) and the elderly. Among these subunit-based vaccines, the viral envelope glycoproteins show great potential as antigens. Areas covered: In this review, progress in the development of safe and effective subunit RSV vaccines based on the viral envelope glycoproteins and intended for pregnant women and the elderly, are reviewed and discussed. Studies published in the period 2012-2018 were included. Expert opinion: Researchers are close to bringing safe and effective subunit-based RSV vaccines to the market using the viral envelope glycoproteins as antigens. However, it remains a major challenge to elicit protective immunity, with a formulation that has sufficient (storage) stability. These issues may be overcome by using the RSV fusion protein in its pre-fusion conformation, and by formulating this protein as a dry powder. It may further be convenient to administer this powder via the pulmonary route.

Dr Simon B. Drysdale, Consultant and Honorary Senior Lecturer in Paediatric Infectious Diseases at St. George's University Hospitals NHS Foundation Trust and St. George's, University of London, is one of the most talented early career academic specialists in Paediatric Infectious Diseases in the United Kingdom. His main research interest is respiratory syncytial virus (RSV); he is particularly interested in understanding the host susceptibility to RSV, the management of RSV infection and associated health economics and the development of treatments and immunisations/vaccines, which are currently lacking. According to Dr Drysdale, RSV is a significant cause of morbidity and mortality among young infants and older adults, particularly those with co-morbidities. While there is ample RSV epidemiological and healthcare cost data available for young infants and children, more data is required for older children and adults. There are currently several antiviral medications for the treatment of RSV infection in development; however, none have yet progressed beyond Phase 2 clinical trials. Multiple types of novel therapeutic molecules have been developed, including fusion and non-fusion inhibitors and polymerase inhibitors aimed at various RSV targets, such as the F protein and RNA polymerase. In recent years, great strides have been made with regards to an RSV vaccine or monoclonal antibody, with >40 candidates currently in development. A maternal RSV vaccine, which just completed a Phase 3 trial, was shown to have 44% efficacy against hospitalization for RSV lower respiratory tract infection in infants. A new long-acting monoclonal antibody against RSV infection, having shown excellent promise in a Phase 2 trial in infants, is about to be investigated in a Phase 3 clinical trial commencing shortly.

Background: Infections with respiratory syncytial virus (RSV) cause significant morbidity and hospitalization in older adults. We studied the humoral, mucosal and B cell responses of an investigational adjuvanted RSV sF vaccine, MEDI7510, in older adults. Methods: In a substudy of a randomized (1:1), double-blind, placebo-controlled study of MEDI7510 in adults ≥60 years of age, we collected blood and nasal secretions at days 0, 8, 29, 91 and 180 post-vaccination to measure F-specific IgG and IgA antibodies by ELISA, and plasmablasts and memory B cells by IgA/IgG dual-color fluorospot. Results: The 27 vaccine- and 18 placebo-recipients had a mean age of 73 years and included 24 women. Among vaccinees, 93% had significant increases in F-specific plasma IgG 85% had increased plasma IgA; 74% had increased nasal IgG and 26% nasal IgA; 93% had IgG and 89% IgA plasmablasts on Day 8 post-immunization; and 82% had IgG and 7.4% IgA memory B cell responses to the vaccine. Vaccinees

Respiratory syncytial virus (RSV) infections peak during the winter months in the United States, yet the timing, intensity, and onset of these outbreaks vary each year. An RSV vaccine is on the cusp of being released; precise models and accurate forecasts of RSV epidemics may prove vital for planning where and when the vaccine should be deployed. Accurate forecasts with sufficient spatial and temporal resolution could also be used to support the prevention or treatment of RSV infections. Previously, we developed and validated an RSV forecast system at the regional scale in the United States. This model-inference system had considerable forecast skill, relative to the historical expectance, for outbreak peak intensity, total outbreak size, and onset, but only marginal skill for predicting the timing of the outbreak peak. Here, we use a superensemble approach to combine three forecasting methods for RSV prediction in the US at three different spatial resolutions: national, regional, and state. At the regional and state levels, we find a substantial improvement of forecast skill, relative to historical expectance, for peak intensity, timing, and onset outbreak up to two months in advance of the predicted outbreak peak. Moreover, due to the greater variability of RSV outbreaks at finer spatial scales, we find that improvement of forecast skill at the state level exceeds that at the regional and national levels. Such finer scale superensemble forecasts may be more relevant for effecting local-scale interventions, particularly in communities with a high burden of RSV infection. Keywords: RSV, Superensemble, Forecast, Infectious disease, Bayesian modeling, Outbreaks, Epidemics, Computational biology

Since the development of the first vaccine against smallpox over two centuries ago, vaccination strategies have been at the forefront of significantly impacting the incidences of infectious diseases globally. However, the increase in the human population, deforestation and climate change, and the rise in worldwide travel have favored the emergence of new viruses with the potential to cause pandemics. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is a cruel reminder of the impact of novel pathogens and the suboptimal capabilities of conventional vaccines. Therefore, there is an urgent need to develop new vaccine strategies that allow the production of billions of doses in a short duration and are broadly protective against emerging and re‐emerging infectious diseases. Extensive knowledge of the molecular biology and immunology of adenoviruses (Ad) has favored Ad vectors as platforms for vaccine design. The Ad‐based vaccine platform represents an attractive strategy as it induces robust humoral and cell‐mediated immune responses and can meet the global demand in a pandemic situation. This review describes the status of Ad vector‐based vaccines in preclinical and clinical studies for current and emerging respiratory viruses, particularly coronaviruses, influenza viruses and respiratory syncytial viruses., This article describes the unique features of adenoviral (Ad) vector‐based vaccine platforms, activation of innate immunity leading to the development of balanced humoral and cell‐mediated immune responses, and potential drawbacks and their circumvention strategies. The progress of Ad vector‐based vaccines for coronaviruses, influenza viruses and respiratory syncytial viruses are discussed in detail.

Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking. Methods This systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as “Respiratory Syncytial Virus, Human,” “Respiratory Syncytial Virus Infections,” “Respiratory Syncytial Virus Vaccines,” “Immunization,” “Immunization Programs” and “Vaccines” and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV‐associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. Results Of 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live‐attenuated/chimeric (n = 14), recombinant‐vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine‐related increased MAARI during RSV surveillance season. Conclusion LID ∆M2‐2, MEDI M2‐2, RSVcps2 and LID/∆M2‐2 /1030s (live‐attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.

Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections in infants and the second most frequent cause of death during the first year of life. This highly contagious seasonal virus is responsible for approximately 3 million hospitalizations and 120,000 deaths annually among children under the age of 5 years. Bronchiolitis is the most common severe manifestation; however, RSV infections are associated with an increased long-term risk for recurring wheezing and the development of asthma. There is an unmet need for new agents and a universal strategy to prevent RSV infections starting at the time of birth. RSV is active between November and April in Italy, and prevention strategies must ensure that all neonates and infants under 1 year of age are protected during the endemic season, regardless of gestational age at birth and timing of birth relative to the epidemic season. Approaches under development include maternal vaccines to protect neonates during their first months, monoclonal antibodies to provide immediate protection lasting up to 5 months, and pediatric vaccines for longer-lasting protection. Meanwhile, improvements are needed in infection surveillance and reporting to improve case identification and better characterize seasonal trends in infections along the Italian peninsula. Rapid diagnostic tests and confirmatory laboratory testing should be used for the differential diagnosis of respiratory pathogens in children. Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations.

Background Mathematical models of respiratory syncytial virus (RSV) transmission can help describe seasonal epidemics and assess the impact of potential vaccines and immunoprophylaxis with monoclonal antibodies (mAb). Methods We developed a deterministic, compartmental model for RSV transmission, which was fitted to population-based RSV hospital surveillance data from Auckland, New Zealand. The model simulated the introduction of either a maternal vaccine or a seasonal mAb among infants aged less than 6 months and estimated the reduction in RSV hospitalizations for a range of effectiveness and coverage values. Results The model accurately reproduced the annual seasonality of RSV epidemics in Auckland. We found that a maternal vaccine with effectiveness of 30–40% in the first 90 days and 15–20% for the next 90 days could reduce RSV hospitalizations by 18–24% in children younger than 3 months, by 11–14% in children aged 3–5 months, and by 2–3% in children aged 6–23 months. A seasonal infant mAb with 40–60% effectiveness for 150 days could reduce RSV hospitalizations by 30–43%, 34–48% and by 14–21% in children aged 0–2 months, 3–5 months and 6–23 months, respectively. Conclusions Our results suggest that either a maternal RSV vaccine or mAb would effectively reduce RSV hospitalization disease burden in New Zealand. Overall, a seasonal mAb resulted in a larger disease prevention impact than a maternal vaccine.

Respiratory syncytial virus (RSV), for which there is currently no licensed vaccine, displays a fusion (F) protein that is considered a vaccine target. This protein has an antigenic site called site O, which has been shown to elicit potent, neutralizing antibodies and has therefore been considered important in the formulation of RSV vaccines. However, this site is also the least conserved region on the F protein across RSV subtypes. Therefore, directing the immune response away from site O and refocusing it toward more conserved parts of the RSV F protein might serve to better elicit broadly neutralizing antibodies. To demonstrate that directing the immune response away from site O is a viable approach, a prefusion F-based vaccine based on an F protein with a shielded site O is generated. Sera from mice immunized with multivalent scaffolds presenting this immunogen is capable of neutralizing RSV of both subtypes. This result may have application in the development of an effective and broadly protective RSV vaccine.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in children worldwide and is a significant cause of hospital admissions in young children in England. No RSV vaccine has been licensed but a number are under development. In this work, we present two structurally distinct mathematical models, parameterized using RSV data from the UK, which have been used to explore the effect of introducing an RSV paediatric vaccine to the National programme. We have explored different vaccine properties, and dosing regimens combined with a range of implementation strategies for RSV control. The results suggest that vaccine properties that confer indirect protection have the greatest effect in reducing the burden of disease in children under 5 years. The findings are reinforced by the concurrence of predictions from the two models with very different epidemiological structure. The approach described has general application in evaluating vaccine target product profiles. Keywords: RSV, Transmission model, RSV vaccination strategies, UK

Respiratory syncytial virus (RSV) is a major cause of severe respiratory tract infection worldwide. but tThere is a monoclonal antibody, palivizumab, which can be used for prophylaxis, butis no licensed vaccine or clinically effective antiviral therapy. The development of an effective vaccine has been hampered over the last 50 years by a medical disastersignificant difficulties in the 1960s in which a formalin-inactivated vaccine led to increased severity of RSV disease following acquisition of the virus in the RSV season after vaccination. However, renewed efforts to develop a vaccine have resulted in up to 445 candidate vaccines and monoclonal antibodies now being in pre-clinical or clinical development (as of December 2018April 2019). The target populations for effective vaccination are varied and include neonates, young children, pregnant women and older adults. The reasons for susceptibility to infection in each of these groups may be different and could therefore require different vaccine types for induction of protective responses, adding a further challenge for vaccine development. Here we review the current knowledge of vaccine development for these target populations, and we propose a view of the priorities for RSV vaccines and their rationale.

Respiratory syncytial virus (RSV) often causes respiratory illness in adults. Over 40 RSV vaccine and monoclonal antibody products are currently in preclinical development or clinical trials. Because RSV diagnostic practices may impact disease burden estimates, we investigated infectious disease physicians' RSV diagnostic practices among their adult patients.

Respiratory syncytial virus (RSV) is a global human pathogen responsible for lower respiratory tract infections (LRTI). While RSV infection is innocuous in healthy adults, it is the leading cause of infant hospitalization for respiratory tract infection. Nearly everyone shows evidence of an RSV infection by the age of 3. However, there is still not a vaccine commercially available. This review will provide an update on the clinical and preclinical vaccine studies and different approaches to prevent RSV infection. Novel vaccine approaches that induce protection against RSV without enhancement of respiratory tract disease. Recent technological approaches have led to generation of different strategies to prevent RSV infection, including live attenuated, chimeric, and subunit vaccines, virus-like particles, and nanoparticles. These vaccine approaches represent promising candidates towards an efficient RSV vaccine that effectively protects infants, children, and adults.

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Lower respiratory tract infection due to RSV is one of the most common causes of hospitalization for infants, especially those born premature or with chronic lung or heart disease. Furthermore, RSV infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals. The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma. RSV was discovered more than 50 years ago, and despite extensive research to identify pharmacological therapies, the most effective management of this infection remains supportive care. The trial of a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe illness upon natural infection. Currently, Palivizumab is the only available option for RSV prophylaxis, and because of restricted clinical benefits and high costs, it has been limited to a group of high-risk infants. There are several ongoing trials in preclinical, Phase-I, Phase-II, or Phase-III clinical stages for RSV vaccine development based on various strategies. Here we review the existing available prophylactic options, the current stages of RSV vaccine clinical trials, different strategies, and major hurdles in the development of an effective RSV vaccine.

Respiratory syncytial virus (RSV) causes lower respiratory tract illness frequently. No effective antivirals or vaccines for RSV are approved for use in the United States; however, there are at least 50 vaccines and monoclonal antibody products in development, with those targeting older adults and pregnant women (to protect young infants) in phase 2 and 3 clinical trials. Unanswered questions regarding RSV epidemiology need to be identified and addressed prior to RSV vaccine introduction to guide the measurement of impact and future recommendations. The Centers for Disease Control and Prevention (CDC) convened a technical consultation to gather input from external subject matter experts on their individual perspectives regarding evidence gaps in current RSV epidemiology in the United States, potential studies and surveillance platforms needed to fill these gaps, and prioritizing efforts. Participants articulated their individual views, and CDC staff synthesized individuals' input into this report.

Major progress is being made in vaccines against Respiratory Syncytial Virus (RSV), with multiple vaccine candidates currently in the clinical phase of development. Making an investment case for public sector financing of RSV vaccine will require estimation of burden, cost-effectiveness and impact. The aim of this study is to determine the proportion, age distribution and clinical spectrum of RSV associated hospitalizations in children in Karachi, Pakistan. A three years prospective study was conducted at the Aga Khan University hospital in Karachi, a city of 20 million in south Pakistan, from August 2009 to June 2012. Children less than five years old admitted with acute respiratory infections (ARI) were enrolled. Throat swabs were collected and tested for RSV using real-time PCR. Multivariable log binomial regression analysis was performed to identify the associated factors of RSV infection. Out of 1150 children enrolled, RSV was detected among 223 (19%). Highest rate of RSV detection was in young infants less than 3 months of age (48/168, 29%), which accounted for 22% of all RSV detected. Most common diagnosis in RSV positive infants (

Over six decades after respiratory syncytial virus (RSV) was recognized as a significant human pathogen, an effective vaccine against it has remained elusive. RSV vaccine development has been hindered by early vaccine approaches that caused enhanced illness and the immunological challenges associated with populations that have the highest burden of severe RSV disease: the very young and the elderly. Recent developments in the understanding of the structure of the RSV fusion protein and dissection of neutralizing antibody responses have provided new insights into previous vaccine failures and have identified key aspects of protection, reinvigorating the RSV vaccine field. Several approaches tailored to protect high-risk target populations are competing in the current pipeline, raising the prospects for licensure of candidate vaccines for active immunization against RSV in the foreseeable future.

In this issue of Immunity, Goodwin et al. (2018) offer hope for an RSV vaccine for young infants by demonstrating that RSV infection in very young infants induces neutralizing antibodies that are close to the germline and have unusual epitope specificity.

Respiratory syncytial virus (RSV) has eluded active vaccination efforts for more than five decades and continues to cause substantial morbidity and mortality in infants, the immunocompromised, and older adults. Although newer approaches of passive antibody-mediated protection show promise, vaccines aimed at eliciting fusion protein (F)-targeting antibodies have repeatedly failed to meet pre-established, modest-efficacy goals. Newer candidates, including protein-based vaccines, live-attenuated viruses, and gene-based delivery platforms, incorporate structurally defined and stabilized versions of the prefusion form of the F glycoprotein and are advancing rapidly into critical efficacy studies in susceptible target populations. This review discusses the storied history of RSV vaccine development, immunological lessons learned along the way, and critical findings about protein structure that remodeled our understanding of protective immunity to this important pathogen.

Respiratory Syncytial Virus (RSV), a leading cause of lower respiratory tract illness, has been a focus of vaccine development efforts in recent years. RSV neutralisation assays are particularly useful in the evaluation of immunogenicity of RSV vaccine candidates. Here we report a collaborative study that was conducted with the aim to establish the 1st International Standard for antiserum to RSV, to enable the standardisation of results across multiple assay formats. Two candidate standards were produced from serum samples donated by healthy adult individuals. 25 laboratories from 12 countries, including university laboratories, manufacturers/developers of RSV vaccines and public health laboratories, participated in the study. The study samples comprised the two candidate standards, NIBSC codes 16/284 and 16/322, naturally infected adult sera, age stratified naturally infected paediatric sera, sera from RSV vaccine clinical trials in maternal and elderly subjects, a monoclonal antibody to RSV (palivizumab), two cotton rat serum samples and samples from the BEI Resources panel of human antiserum and immune globulin to RSV. The collaborative study showed that between-laboratory variability in neutralisation titres was substantially reduced when values were expressed relative to those of either of the two candidate international standards. Stability of 16/284 and 16/322 maintained for 6 months at different temperatures showed no significant loss of activity (relative to that at −20 °C storage temperature) at temperatures of up to +20 °C. Based on these results, 16/284 was established as the 1st International Standard for antiserum to RSV, with an assigned unitage of 1000 International Units (IU) of anti-RSV neutralising antibodies per vial, by the WHO Expert Committee on Biological Standardisation, with 16/322 suitable as a possible replacement standard for 16/284.

Respiratory syncytial virus-specific neutralizing antibodies (RSV NAbs) are an important marker of protection against RSV. A number of different assay formats are currently in use worldwide so there is a need for an accurate and high-throughput method for measuring RSV NAbs. We describe here an imaging-based micro-neutralization assay that has been tested on RSV subgroup A and can also be adapted for RSV subgroup B and different sample types. This method is highly reproducible, with inter-assay variations for the reference antiserum being less than 10%. We believe this assay can be readily established in many laboratories worldwide at relatively low cost. Development of an improved, high-throughput assay that measures RSV NAbs represents a significant step forward for the standardization of this method internationally as well as being critical for the evaluation of novel RSV vaccine candidates in the future.

Respiratory syncytial virus (RSV) infection is responsible for one-third of deaths of acute lower respiratory infection in children less than one-year-old. The formaldehyde-inactivated RSV vaccine trial conducted in the 1960s predisposed the vaccinees to more serious RSV infection instead of protection. Better understanding of the underlying mechanism is of critical importance for better designing of safe and effective RSV vaccines. Areas covered: PubMed was searched to review immunopathology induced by RSV vaccines. We intend to dissect the differences in clinical and pathological manifestations of enhanced respiratory disease (ERD) in different animal models in comparison with humans. Formaldehyde-inactivated RSV vaccine causes ERD in both humans and animals, while RSV vaccine without formaldehyde treatment could also induce similar disease in animals, suggesting multiple pathways may be involved. Expert commentary: Identification of biomarkers pertinent to clinical evaluation should be further explored for safety assessment of RSV vaccines in human trials.

Respiratory syncytial virus (RSV) is an important cause of viral lower respiratory tract illness in infants and children globally, but no vaccine is currently available to protect these vulnerable populations. Live-attenuated vaccine approaches have been in development for decades, but achieving the appropriate balance between immunogenicity and safety has proven difficult. Immunoprophylaxis with the neutralizing monoclonal antibody palivizumab is limited to high-risk infants, but cost requirements for multiple dosing make its use impractical in low- and middle-income countries. A growing number of RSV vaccine candidates using a variety of technologies and targeting diverse populations has emerged in recent years. There are now 60 RSV vaccine candidates in development that target pediatric and elderly populations. While most are at a preclinical stage, 16 candidates are in clinical development. This review summarizes current RSV vaccine research and development, including an overview of the vaccine platforms being used, the development stage of individual vaccine candidates, and gaps to be addressed to facilitate use of these vaccines to meet global health needs.

Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infections in young children. Globally, there is huge disease burden, high treatment cost, and health impact beyond acute episodes due to RSV which necessitate development and implementation of preventive strategies for the control of RSV infection. The disease burden due to RSV in pediatric population across India is still not clearly understood so this literature review was therefore conducted to gather data on disease burden due to RSV in Indian pediatric population. Systematic literature search was performed using PubMed and Google search with different medical subject headings from 2007 to 2020. Studies performed in Indian pediatric population were selected for review. Literature review revealed that in India, epidemiology of RSV infection is well documented in young children (0-5 years) as compared to children from other age groups. The rates of RSV detection in various studies conducted in younger children (0-5 years) vary from 2.1% to 62.4% in India which is higher as compared to children from other age groups. In India, RSV mainly peaks around rainy to early winter season, that is, during months of June through October while smaller peak was noted during December, January, and February. In 2020, higher RSV-associated disease burden was reported among children (

Objectives There are no approved vaccines for respiratory syncytial virus (RSV), and consensus on methods to assess RSV vaccine efficacy has not been established. In this study of an adjuvanted RSV vaccine, we evaluated an RSV disease endpoint using a patient-reported outcome instrument (the inFLUenza Patient-Reported Outcome instrument [FLU-PRO]) and molecular testing for virologic confirmation. Methods In a randomized, blinded efficacy study (NCT02508194), 1900 adult participants aged ≥60 years who had any respiratory symptom lasting ≥24 hours recorded symptoms in a FLU-PRO–based workbook for 21 days, self-collected nasal swabs on illness days 2 to 4, and had a site-collected swab obtained on (approximately) day 4. The endpoint, acute RSV-associated respiratory illness (ARA-RI), required specific symptoms with virologic confirmation. Results The FLU-PRO demonstrated reliability, ability to detect change, and validity and had high participant adherence and acceptable patient burden in the setting of an RSV prevention trial. The ARA-RI endpoint definition captured all 33 virologically confirmed RSV illnesses for which symptom data were provided, and in 32 of these, at least 1 lower respiratory symptom was reported. Sensitivity analysis with an endpoint requiring ≥2 lower respiratory symptoms captured greater symptom severity but fewer cases. Results of self- and site-collected swabs were highly correlated. Self-swabbing detected 9 additional cases that would have been missed by site swabbing only. Conclusions These results demonstrated the reliability and validity of the ARA-RI definition and of the FLU-PRO for use in RSV studies. Self-swabbing improved RSV detection.

Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHADA (R) adjuvant.Virosomes were initially formed by contacting a lipid film containing 3D-PHADA (R) with viral membranes solubilized with the short chain phospholipid DCPC, followed by dialysis, later by adding solubilized 3D-PHAD to viral membranes, or to preformed virosomes from DMSO.Virosomes formed from lipid films contained the membrane glycoproteins G and F, at similar F to G ratios but lower concentrations than in virus, and the added lipids, but only a fraction of the 3D-PHADA (R). By single particle tracking (SPT), the virosome size distribution resembled that seen by cryo-electron microscopy, but dynamic light scattering showed much larger particles. These differences were caused by small virosome aggregates. Measured by SPT, virosomes were stable for 300 days. 3DPHAD A (R) incorporation in virosomes could be enhanced by providing the adjuvant from DCPC solubilized stock, but also by adding DMSO dissolved adjuvant to pre-formed virosomes. Virosomes with 0.1 mg/mg of 3D-PHADA (R)/viral protein from DMSO induced antibody titers similar to those by virosomes containing 0.2 mg/mg of DCPC-solubilized 3D-PHADA (R).Stable 3D-PHADA (R) adjuvanted RSV virosomes can be formulated.

A number of vaccines against Respiratory Syncytial Virus (RSV) infection are approaching licensure. Deciding which RSV vaccine strategy, if any, to introduce, will partly depend on cost-effectiveness analyses, which compares the relative costs and health benefits of a potential vaccination programme. Health benefits are usually measured in Quality Adjusted Life Year (QALY) loss, however, there are no QALY loss estimates for RSV that have been determined using standardised instruments. Moreover, in children under the age of five years in whom severe RSV episodes predominantly occur, there are no appropriate standardised instruments to estimate QALY loss. We estimated the QALY loss due to RSV across all ages by developing a novel regression model which predicts the QALY loss without the use of standardised instruments. To do this, we conducted a surveillance study which targeted confirmed episodes in children under the age of five years (confirmed cases) and their household members who experienced symptoms of RSV during the same time (suspected cases.) All participants were asked to complete questions regarding their health during the infection, with the suspected cases aged 5–14 and 15+ years old additionally providing Health-Related Quality of Life (HR-QoL) loss estimates through completing EQ-5D-3L-Y and EQ-5D-3L instruments respectively. The questionnaire responses from the suspected cases were used to calibrate the regression model. The calibrated regression model then used other questionnaire responses to predict the HR-QoL loss without the use of EQ-5D instruments. The age-specific QALY loss was then calculated by multiplying the HR-QoL loss on the worst day predicted from the regression model, with estimates for the duration of infection from the questionnaires and a scaling factoring for disease severity. Our regression model for predicting HR-QoL loss estimates that for the worst day of infection, suspected RSV cases in persons five years and older who do and do not seek healthcare have an HR-QoL loss of 0·616 (95% CI 0·155–1·371) and 0·405 (95% CI 0·111–1·137) respectively. This leads to a QALY loss per RSV episode of 1·950 × 10−3 (95% CI 0·185 × 10−3 –9·578 × 10−3) and 1·543 × 10−3 (95% CI 0·136 × 10−3 –6·406 × 10−3) respectively. For confirmed cases in a child under the age of five years who sought healthcare, our model predicted a HR-QoL loss on the worst day of infection of 0·820 (95% CI 0·222–1·450) resulting in a QALY loss per RSV episode of 3·823 × 10−3 (95% CI 0·492 × 10−3 –12·766 × 10−3). Combing these results with previous estimates of RSV burden in the UK, we estimate the annual QALY loss of healthcare seeking RSV episodes as 1,199 for individuals aged five years and over and 1,441 for individuals under five years old. The QALY loss due to an RSV episode is less than the QALY loss due to an Influenza episode. These results have important implications for potential RSV vaccination programmes, which has so far focused on preventing infections in infants—where the highest reported disease burden lies. Future potential RSV vaccination programmes should also evaluate their impact on older children and adults, where there is a substantial but unsurveilled QALY loss.

A safe and effective vaccine against RSV remains an important unmet public health need. Intranasally (IN) delivered live-attenuated vaccines represent the most extensively studied approach for immunization of RSV-naive infants and children, however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we report pre-clinical immunogenicity and efficacy data utilizing a live-attenuated vaccine candidate, RGΔM2-2, which was obtained by deleting the M2-2 open reading frame from the genome of the MSA1 clinical isolate. Intramuscular (IM) administration of RGΔM2-2 in cotton rats induced immunity and protective efficacy that was comparable to that induced by intranasal (IN) immunization. In contrast, the protective efficacy of RGΔM2-2 delivered by the IM route to African green monkeys was substantially reduced as compared to the efficacy following IN administration, despite comparable levels of serum neutralizing antibodies. This result suggests that mucosal immunity may play an important role in RSV protection. The RGΔM2-2 vaccine also demonstrated different attenuation profiles when tested in cotton rats, non-human primates, and a human airway epithelial (HAE) cell model. The data suggest RGΔM2-2 is less attenuated than a similarly designed vaccine candidate constructed on the A2 genetic background. These findings have important implications with regard to both the design and the preclinical safety testing of live-attenuated 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.

Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections (LRTI) in infants, the elderly, and the immunocompromised. Although the development of a RSV vaccine has been a priority for50 years, there is still no vaccine available. Treatment of RSV LRTI has remained mostly supportive, i.e. hydration and oxygenation. Palivizumab and ribavirin are the only options currently available for prevention and treatment of RSV infection, but evidence suggests that they are not fully effective. This creates a significant unmet medical need for new therapeutics for prevention and treatment of RSV worldwide. Areas covered: This article reviews the antiviral drugs and monoclonal antibodies (mAb) for RSV that are in different stages of clinical development. Expert commentary: Over the last 10 years, new antiviral drugs and mAb have shown clinical promise against RSV, and may become available in the coming years. Although the RSV fusion protein has been the most popular target for inhibitors and mAbs, new approaches targeting other viral proteins have shown promising results. To overcome the emergence of RSV escape mutants, combination antiviral therapy may be explored in the future.

2017 will mark the 60(th) anniversary since the first isolation of RSV in children. In spite of concerted efforts over all these years, the goal of developing an effective vaccine against paediatric RSV disease has remained elusive. One of the main hurdles standing in the way of an effective vaccine is the fact that the age incidence of severe disease peaks within the first 3 months of life, providing limited opportunity for intervention. In addition to this complexity, the spectre of failed historical vaccines, which increased the risk of illness and death upon subsequent natural infection, has substantially increased the safety criteria against which modern vaccines will be assessed. This review traces the history of RSV vaccine development for young infants and analyses the potential reasons for the failure of historic vaccines. It also discusses recent breakthroughs in vaccine antigen design and the progressive evolution of platforms for the delivery of these antigens to seronegative infants.

ObjectivesThis study aims to describe the burden of respiratory syncytial virus (RSV) in children