A study recently published in the journal PLoS One revealed a promising new vaccine strategy against infection with the human respiratory syncytial virus (RSV) in rats. The study is entitled “Mammalian Cell-Derived Respiratory Syncytial Virus-Like Particles Protect the Lower as well as the Upper Respiratory Tract,” and was conducted by researchers at John A. Burns School of Medicine, University of Hawaii at Manoa and Emory University in Atlanta, Georgia.
Human RSV is a negative-stranded RNA virus belonging to the genus Pneumovirus. RSV is a major cause of severe lower respiratory tract infections in infants, being the leading cause of pneumonia and bronchiolitis (inflammation of the small airways in the lung) in children younger than one year of age. It is estimated that RSV is responsible for 85,000 to 144,000 infant hospitalizations every year in the United States. The virus also causes a significant morbidity in the elderly population, immunocompromised individuals and those with cardiopulmonary disease. Currently there is no licensed vaccine or effective treatment for RSV disease.
In the study, researchers tested the vaccine potential of native RSV virus-like particles (RSV VLPs) derived from mammalian cells. VLPs are safe, recombinantly generated particles composed of several copies of selected proteins, in this case three proteins from RSV – the surface glycoproteins G and F, which contain many T cell and antibody neutralizing epitopes, and the matrix protein M, important for morphogenesis.
Researchers found that in vitro, VLPs were functionally assembled and immunoreactive. Furthermore, the recombinant F protein was processed in a way similar to the natural viral F protein leading to the production of F1 and F2 subunits. The F1 subunit is crucial for vaccine development as it contains all the neutralizing epitopes present in the F protein. Remarkably, rats vaccinated with two doses of RSV VLPs [using monophosphoryl lipid A (MPLA) and alum as adjuvants to enhance immunogenicity] developed a strong neutralizing antibody response and were protected from viral infection in both the lower and upper respiratory tract. According to the authors, this is the first VLP/virosome vaccine study that resulted in a protective effect on the lower but also the upper respiratory tract.
The research team concluded that their alum/MPLA adjuvanted RSV VLPs conferred protection to rats offering a significant virus clearance from the lung and nose. The team suggests that RSV VLPs might represent a novel safe and effective vaccine approach against RSV infection.
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