Ongoing developments in RSV prophylaxis: a clinician’s analysis (original) (raw)
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Review of palivizumab in the prophylaxis of respiratory syncytial virus (RSV) in high-risk infants
Biologics: targets & therapy, 2008
In respiratory syncytial virus (RSV) disease the balance between the innate and adaptive immune responses determines the expression of the pathological phenotype favoring the development of acute bronchiolitis, and in certain children the development of recurrent wheezing. While humoral antibody plays a major role in protection against disease, T-cell immunity targeted to viral proteins appears to terminate viral infection. At the moment, treatment modalities for acute RSV infection do not effectively modify the course of the disease, and RSV vaccine development has shown conflicting results. To date, however, passive immunoprophylaxis with monoclonal antibodies is the only strategy that has demonstrated consistent efficacy in reducing RSV hospitalizations in high-risk children. The potential benefit of new strategies for prevention and treatment of RSV infections should be evaluated with respect to both the acute infection as well as the chronic respiratory manifestations induced by RSV.
Recent Trends in RSV Immunoprophylaxis: Clinical Implications for the Infant
American Journal of Perinatology, 2019
Respiratory syncytial virus (RSV) remains the leading cause for hospitalizations in infants worldwide, resulting in significant health and financial burden. Since 1998, the humanized monoclonal antibody palivizumab remains the only available option licensed for the prevention of severe RSV disease in high-risk children, namely premature infants and those with chronic lung disease and congenital heart disease. In 2014, the American Academy of Pediatrics modified the recommendations on the use of RSV prophylaxis in these high-risk children, and limited its use to premature infants born at < 28 weeks' gestational age (wGA). Following this last guidance update, studies have confirmed that premature infants of 29 to 34 wGA remain at high risk for severe RSV disease, especially those of younger chronologic age. New and more cost-effective strategies are being developed that would help alleviate both the health and financial burden associated with severe RSV disease.
Pharmacologic Advances in the Treatment and Prevention of Respiratory Syncytial Virus
Clinical Infectious Diseases, 2010
Currently, only 2 drugs have been approved for the treatment of respiratory syncytial virus (RSV). Palivizumab is a monoclonal antibody for the prevention of RSV in high-risk children. Ribavirin is approved for treatment of severe RSV disease; however, its effectiveness in improving outcomes is questionable. During the past 40 years, many obstacles have delayed the development of safe and effective vaccines and treatment regimens. This article reviews these obstacles and presents the novel development strategies used to overcome many of them. Also discussed are promising new antiviral treatment candidates and their associated mechanism of action, the significant advances made in vaccine development, and exciting, new studies directed at improving outcomes through pharmacologic manipulation of the host response to RSV disease. Respiratory syncytial virus (RSV) is the leading cause of pediatric viral respiratory tract infections. The World Health Organization estimates an annual mortality rate of ∼160,000 deaths worldwide [1]; more inclusive all-cause mortality rates related to RSV approach 600,000 deaths [2]. RSV is also the second leading cause of viral death in elderly individuals [3]. By 18 months of age, 87% of children have developed RSVspecific antibodies [4]; by 3 years of age, virtually all children have been infected. In the United States alone, RSV infection results in 1120,000 childhood hospitalizations and up to 500 deaths [5]. Compared with influenza, RSV accounts for 19 times more deaths in children younger than 1 year [6-11]. Only 2 US Food and Drug Administration (FDA)-approved drugs are currently available for RSV disease. Palivizumab is indicated for RSV prevention in high-risk infants, including those with chronic lung disease, those with congenital heart disease, and those born prematurely [12]. This indication is based on hospitalization rates that are ∼5 times greater in highrisk versus non-high-risk infants. However, among all infants hospitalized with severe RSV disease, ∼70% are term infants
Respiratory syncytial virus: current and emerging treatment options
ClinicoEconomics and Outcomes Research, 2014
Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and children worldwide. Although RSV typically causes mild upper respiratory infections, it frequently causes severe morbidity and mortality, especially in premature infants and children with other chronic diseases. Treatment of RSV is limited by a lack of effective antiviral treatments; however, ribavirin has been used in complicated cases, along with the addition of intravenous immune globulin in specific patients. Vaccination strategies for RSV prevention are heavily studied, but only palivizumab (Synagis ®) has been approved for use in the United States in very select patient populations. Research is ongoing in developing additional vaccines, along with alternative therapies that may help prevent or decrease the severity of RSV infections in infants and children. To date, we have not seen a decrement in RSV morbidity and mortality with our current options; therefore, there is a clear need for novel RSV preventative and therapeutic strategies. In this review, we discuss the current and evolving trends in RSV treatment for infants and children.
Archives of Disease in Childhood, 2014
In most high-income countries palivizumab prophylaxis is considered safe, efficacious and cost-effective for preventing respiratory syncytial virus (RSV) hospital admissions among specific subgroups of infants born preterm, with chronic lung disease or with congenital heart disease. Virtually all babies acquire RSV during infancy and previously healthy babies are not eligible to receive palivizumab. Emerging evidence suggests some benefit of palivizumab use in reducing recurrent wheeze among infants born preterm. Better longitudinal studies are needed to examine its clinical and cost-effectiveness on recurrent and chronic respiratory illness and associated healthcare burden on resources in the community and hospitals. Since 99% of child deaths attributed to RSV occur in resource poor countries where expensive prophylaxis is not available or affordable, palivizumab has limited potential to impact on the current global burden of RSV lower respiratory tract infection (LRTI). A range of candidate vaccines for active immunisation against RSV are now in clinical trials. Two promising new antivirals are also currently in phase I/II trials to test their effectiveness in preventing severe RSV LRTI. These agents may be effective in preventing severe disease and phase III studies are in development. In the absence of effective active immunisation against RSV infection, population level approaches to prevent severe RSV LRTI should continue to focus on reducing prenatal and environmental risk factors including prematurity, smoking and improving hygiene practices.
Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?
International Journal of Molecular Sciences, 2021
Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, n...
Respiratory syncytial virus prophylaxis—the story so far
Respiratory Medicine, 2002
Respiratory syncytialvirus (RSV) is a common and highlycontagious pathogenthatinfects nearly all children by the age of 2 years.It is responsible for significant morbidity and mortality worldwide among certain high-risk paediatric populations.Therapyis sub-optimal for RSV, thus treatmentfocuses on ameliorating symptoms.Since discoveryofthe virus in the1950s, efforts have been ongoing to develop a safe and effective vaccine.These efforts have met with serious obstacles. Passive immunoprophylaxis presents a viable alternative to active immunization. In 1998, the genetically engineered humanized monoclonal antibody (palivizumab) was granted FDA (Food and Drug Administration) approval for prophylaxis of high-riskchildren in the United States;EMEA (European Agency for the Evaluation of Medicinal Products) approval followed in 1999 for Europe. It is now approved in over 45 countries worldwide. Palivizumab was shown to significantly reduce RSV-related hospitalizations in North America and Europe with few adverse effects.Clinical trial and outcomes data documenting experience with palivizumab to date continue to extend the initial safety and efficacy observations.
A multifaceted approach to RSV vaccination
Human vaccines & immunotherapeutics, 2018
Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. In addition, RSV infections occur throughout different ages, thus, maintaining the virus in circulation, and increasing health risk to more susceptible populations such as infants, the elderly, and the immunocompromised. To date, there is no vaccine approved to prevent RSV infection or minimize symptoms of infection. Current clinical trials for vaccines against RSV are being carried out in four very different populations. There are vaccines that target two different pediatric populations, infants 2 to 6 month of age and seropositive children over 6 months of age, as well as women (non-pregnant or pregnant in their third trimester). There are vaccines that target adult and elderly populations. In this review, we will present and discuss RSV vaccine candidates currently in clinical trials. We will describe the preclinical studies...