Abstract
Globally, Respiratory Syncytial Virus (RSV) is a leading cause of bronchiolitis and pneumonia in children less than one year of age and in USA alone, between 85,000 and 144,000 infants are hospitalized every year. To date, there is no licensed vaccine. We have evaluated vaccine potential of mammalian cell-derived native RSV virus-like particles (RSV VLPs) composed of the two surface glycoproteins G and F, and the matrix protein M. Results of in vitro testing showed that the VLPs were functionally assembled and immunoreactive, and that the recombinantly expressed F protein was cleaved intracellularly similarly to the virus-synthesized F protein to produce the F1 and F2 subunits; the presence of the F1 fragment is critical for vaccine development since all the neutralizing epitopes present in the F protein are embedded in this fragment. Additional in vitro testing in human macrophage cell line THP-1 showed that both virus and the VLPs were sensed by TLR-4 and induced a Th1-biased cytokine response. Cotton rats vaccinated with RSV VLPs adjuvanted with alum and monophosphoryl lipid A induced potent neutralizing antibody response, and conferred protection in the lower as well as the upper respiratory tract based on substantial virus clearance from these sites. To the best of our knowledge, this is the first VLP/virosome vaccine study reporting protection of the lower as well as the upper respiratory tract: Prevention from replication in the nose is an important consideration if the target population is infants < 6 months of age. This is because continued virus replication in the nose results in nasal congestion and babies at this age are obligate nose breathers. In conclusion, these results taken together suggest that our VLPs show promise to be a safe and effective vaccine for RSV.
Highlights
Human respiratory syncytial virus (RSV) is non-segmented negative-stranded RNA virus in the genus Pneumovirus, subfamily Pneoumovirinae, family Paramyxoviridae
In this study we have used mammalian cells to generate RSV virus-like particles (VLPs) composed of G, F, and M proteins of RSV A2 strain (RSV/A2) virus
It is important to note that the F potein is an essential immunogen for RSV vaccine development, and that all the neutralizing epitopes in RSV F protein are located in this F1 fragment [4]; clearly the presence of this fragment is crucial for vaccine development
Summary
Human respiratory syncytial virus (RSV) is non-segmented negative-stranded RNA virus in the genus Pneumovirus, subfamily Pneoumovirinae, family Paramyxoviridae. It has genes, 3’-NS1, NS2, N, P, M, SH, G, F, M2 and L-5’ encoding proteins. F1 protein induces fusion between the virus and host cell membranes with the release of the genome in to the cell cytoplasm. The G protein binds to heparin-like glycosaminoglycans [1] and the fusion between virus and host cell membranes is facilitated by this attachment. The F protein sequence is relatively conserved among different RSV isolates, and neutralizing antibody to F protein can provide protection against both A and B subgroups [4]. The F and G proteins contain several T cell epitopes and all antibody neutralizing epitopes between them [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
