Selective induction of protection against influenza virus infection in mice by a lipid-peptide conjugate delivered in liposomes.
We have previously reported (Muller et al. Vaccine 1990, 8, 308) that two cyclic peptide analogues called D loop and K loop, corresponding to residues 139-147 in site A of the haemagglutinin (HA) of influenza A virus (strain X31), were both able to provide protective immunity to infected OF1 mice when administered in the form of peptide-ovalbumin conjugates. The predicted conformation of the D loop is nearly identical to that of the native loop known from the X-ray structure of HA, while the predicted conformation of the K loop differs significantly from the native one. In this study, the two peptides were conjugated to small unilamellar liposomes, thus creating a chemically defined immunogen, and OF1 mice were immunized with these liposomes containing monophosphoryl lipid A as adjuvant. Compared with protein carrier systems, the liposomal preparations are completely synthetic and avoid the use of Freund's adjuvant. By using liposomes associated with the D loop, we were able to achieve 70% protection of the mice against intranasal challenge with the influenza virus while no protection was obtained with the liposome-associated K loop. The difference in effect between the two liposome and ovalbumin carrier systems may result from the induction of different structures in the peptides when coupled to lipid anchors than when coupled to proteins.
Friede
M
M
UPR 9021 Immunochimie des Peptides et des Virus, CNRS IBMC, Strasbourg, France.
Muller
S
S
Briand
J P
JP
Plaué
S
S
Fernandes
I
I
Frisch
B
B
Schuber
F
F
Van Regenmortel
M H
MH
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001560:Benzidines / Q000737:chemistry; D002352:Carrier Proteins / Q000378:metabolism; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000276:immunology*; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008081:Liposomes; D051379:Mice; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011487:Protein Conformation; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
D001560:Benzidines; D002352:Carrier Proteins; D004337:Drug Carriers; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D008081:Liposomes; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; C006770:bis(diazo)benzidine