Enhanced immune protection by a liposome-encapsulated recombinant respiratory syncytial virus (RSV) vaccine using immunogenic lipids from Deinococcus radiodurans.
The radiation-resistant bacterium, Deinococcus radiodurans contains a variety of phospho-, glyco- and phosphoglycolipids, the structures of which appear to be largely unique in nature. We show here that such lipids are immunogenic when administered as liposomes intranasally in mice, as evidenced by the induction of serum antibodies which recognize D. radiodurans lipids but not other lipids by thin layer chromatographic immunostaining. By modifying a liposomal vaccine against respiratory syncytial virus (RSV) we find that vaccine efficacy is markedly enhanced by the inclusion of lipids isolated from D. radiodurans. Using dioleoylphosphatidylcholine (DOPC) or D. radiodurans lipids, liposomes were prepared which encapsulated a soluble fragment of the RSV G protein (G(128-188)) fused with a portion of the bacterial thioredoxin (Trx) protein. Mice immunized intranasally with D. radiodurans liposomes showed markedly greater protection against RSV challenge over mice immunized with DOPC liposomes. Enhanced vaccine efficacy was achieved using liposomes prepared from either whole D. radiodurans lipids or from a single isolated phosphoglycolipid previously identified as alpha-galactosylphosphatidylglyceroylalkylamine (lipid 7). Mice immunized and protected against RSV challenge were free of pulmonary eosinophilic infiltration, an undesirable consequence of many RSV vaccines. The results provide further support for liposome-based vaccines for RSV and underline the importance of lipid composition in liposome formulations.
Huang
Yan
Y
Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada B3H 4H7.
Anderson
Robert
R
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001419:Bacteria / Q000276:immunology; D015707:HN Protein / Q000235:genetics / Q000276:immunology; D008055:Lipids / Q000737:chemistry / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009500:Neutralization Tests; D010713:Phosphatidylcholines / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014759:Viral Envelope Proteins
D000914:Antibodies, Viral; D015707:HN Protein; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C116204:attachment protein G; C017251:1,2-oleoylphosphatidylcholine