Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia-Implications for Vaccine Design.

The human respiratory syncytial virus (hRSV) is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th)-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus.

Respiratory syncytial virus vaccines: an update on those in the immediate pipeline.

Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infection among infants and the elderly worldwide. Despite its long history, no licensed vaccine is available. Recently, advances in the knowledge of RSV biology and pathology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines. The aim of this review is to analyze RSV characteristics, to consider the history of RSV vaccines and to discuss RSV vaccines currently in development. Among the candidates in clinical trials, nanoparticle and subunit vaccines seem to be the most promising for pregnant women and the elderly, whereas live-attenuated or vector-based vaccines appear to be optimal for the pediatric population.

RSV--a substantial slice of the airway disease burden and the way to a vaccine.

BACKGROUND: The impact of an active RSV vaccine in the future will depend on the true fraction of airway diseases attributable to RSV as the causal pathogen, since many pathogens contribute to the airway disease burden at the same time. This attributable slice of the airway disease burden can vary between populations, regions and seasons, and by the incidence of co-infections. Furthermore, potential future vaccine effectiveness will depend on several characteristics such as prevention of vaccine escape mutants and earliest possible time of vaccination. AIMS AND METHODS: To analyse the disease burden attributable to RSV and review recently published, high-quality epidemiological data from all parts of the world. The development of an active RSV vaccine is illustrated and hurdles in delivery are described. RESULTS: RSV is estimated to be responsible for up to 22% of severe lower respiratory tract infections in children under 5 years of age. First lifetime RSV infections occur at a very early age, mainly in infants and toddlers, in a seasonal pattern, and lead to bacterial co-infections in about one-third of patients. The development of an active RSV vaccine faces several hurdles such as incomplete natural immunity, high variability of RS viruses, selection of the best antigens, choosing the proper vaccine technology platform, and lack of an immune correlate of protection. Added to this is the long way a clinical development programme has to go before it is possible from a regulatory point of view to test a vaccine candidate in a considerable number of RSV-naive children. CONCLUSION: An active RSV vaccine is urgently needed, but, given experience in the 1960s with the formalin-inactivated vaccines, and the long and complicated process involved in development, considerable support and flexibility by regulatory bodies and substantial funds are needed. The slice of up to 22% of the ARI disease burden in the first 5 years of life, which is potentially preventable by an active vaccine, is substantial, and the endeavour worthwhile.