Publications by authors named "Charles J Sande"

Respiratory syncytial virus (RSV) causes infection throughout life, with infants, adults who are severely immunocompromised, and the elderly at special risk of developing lower respiratory tract disease, hospitalisation, and death. The burden of severe disease in the elderly is comparable to seasonal influenza, and there remains no effective anti-viral drugs or vaccine for any target population. The development of a vaccine to confer immunity against severe disease is a major global health priority.

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The development of an effective vaccine against respiratory syncytial virus (RSV) has been hampered by major difficulties that occurred in the 1960s when a formalin-inactivated vaccine led to increased severity of RSV disease after acquisition of the virus in the RSV season after vaccination. Recent renewed efforts to develop a vaccine have resulted in about 38 candidate vaccines and monoclonal antibodies now in clinical development. The target populations for effective vaccination are varied and include neonates, young children, pregnant women, and older adults.

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Respiratory syncytial virus (RSV) is responsible for a large burden of disease globally and can present as a variety of clinical syndromes in children of all ages. Bronchiolitis in infants under 1 year of age is the most common clinical presentation hospitalizing 24.2 per 1000 infants each year in the United Kingdom.

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RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children.

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Severe disease associated with respiratory syncytial virus (RSV) infection occurs predominantly among infants under 6 months of age. Vaccines for prevention are in clinical development. Assessment of the vaccine effectiveness in large epidemiological studies requires serological assays which are rapid, economical and standardised between laboratories.

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Objectives: Respiratory syncytial virus (RSV) causes respiratory infection across the world, with infants and the elderly at particular risk of developing severe disease and death. The replication-defective chimpanzee adenovirus (PanAd3-RSV) and modified vaccinia virus Ankara (MVA-RSV) vaccines were shown to be safe and immunogenic in young healthy adults. Here we report an extension to this first-in-man vaccine trial to include healthy older adults aged 60-75 years.

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Introduction: Respiratory syncytial virus (RSV) is the single most important cause of severe respiratory illness in infants. There is no effective vaccine and the only effective treatment available is the monoclonal antibody palivizumab which reduces the risk of severe RSV disease in prematurely born infants. However, palivizumab is too costly to allow for wide implementation and thus treatment is restricted to supportive care.

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The upper airway - which consists mainly of the naso- and oro-pharynx - is the first point of contact between the respiratory system and microbial organisms that are ubiquitous in the environment. It has evolved highly specialised functions to address these constant threats whilst facilitating seamless respiratory exchange with the lower respiratory tract. Dysregulation of its critical homeostatic and defence functions can lead to ingress of pathogens into the lower respiratory tract, potentially leading to serious illness.

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2017 will mark the 60 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.

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Background: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in early life and a target for vaccine prevention. Data on the age-prevalence of RSV specific antibodies will inform on optimizing vaccine delivery.

Methods: Archived plasma samples were randomly selected within age strata from 960 children less than 145 months of age admitted to Kilifi County Hospital pediatric wards between 2007 and 2010.

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Background: The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development.

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Respiratory syncytial virus (RSV) infection is ubiquitous with almost all infants having been infected by 2 years of age and lifelong repeated infections common. It is the second largest cause of mortality, after malaria, in infants outside the neonatal period and causes up to 200,000 deaths per year worldwide. RSV results in clinical syndromes that include upper respiratory tract infections, otitis media, bronchiolitis (up to 80% of cases) and lower respiratory tract disease including pneumonia and exacerbations of asthma or viral-induced wheeze.

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Respiratory syncytial virus (RSV) infection is the most important cause of hospitalization in infants and is one of the leading global causes of infant mortality and as such its prevention through vaccination is a public health priority. While essential for the successful implementation of vaccine programs, there remains a paucity of data on the epidemiology of the virus in different settings and age groups and limited knowledge about virus transmission and the health-care costs of the disease. Such data are now needed to populate health economic models and to inform optimal approaches to disease control through vaccination.

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Respiratory syncytial virus (RSV) causes respiratory infection in annual epidemics, with infants and the elderly at particular risk of developing severe disease and death. However, despite its importance, no vaccine exists. The chimpanzee adenovirus, PanAd3-RSV, and modified vaccinia virus Ankara, MVA-RSV, are replication-defective viral vectors encoding the RSV fusion (F), nucleocapsid (N), and matrix (M2-1) proteins for the induction of humoral and cellular responses.

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To determine the age at which infants mount significant neutralising antibody responses to both natural RSV infection and live vaccines that mimic natural infection, RSV-specific neutralising antibodies in the acute and convalescent phase sera of infants with RSV infection were assayed. Age-specific incidence estimates for hospitalisation with severe RSV disease were determined and compared to age-specific neutralising antibody response patterns. Disease incidence peaked at between 2 and 3.

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The effect of genetic variation on the neutralizing antibody response to respiratory syncytial virus (RSV) is poorly understood. In this study, acute- and convalescent-phase sera were evaluated against different RSV strains. The proportion of individuals with homologous seroconversion was greater than that among individuals with heterologous seroconversion among those infected with RSV group A (50% vs 12.

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Background: Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear.

Methods: Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics.

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