Intranasal Protollin-formulated recombinant SARS S-protein elicits respiratory and serum neutralizing antibodies and protection in mice.
The feasibility of developing a prophylactic vaccine against SARS was assessed by comparing the immune responses elicited by immunizing mice with a recombinant SARS spike glycoprotein (S-protein) formulated with different adjuvants, given by different routes. In both young and aged mice, an intranasal Protollin-formulated S-protein vaccine elicited high levels of antigen-specific IgG in serum, comparable to those elicited by an intramuscular Alum-adsorbed S-protein vaccine. Serum antibodies were shown to be virus neutralizing. Intranasal immunization of young mice with the Protollin-formulated vaccine elicited significant levels of antigen-specific lung IgA in contrast to mice immunized with the intramuscular vaccine in which no antigen-specific lung IgA was detected. Following live virus challenge of aged mice, no virus was detected in the lungs of intranasally immunized mice, in contrast to intramuscularly immunized mice whose lung virus titers were comparable to those observed in control mice.
Hu
Mary C
MC
GlaxoSmithKline Biologicals North America of Washington, 19204 North Creek Parkway, Bothell, WA 98011, USA.
Jones
Taff
T
Kenney
Richard T
RT
Barnard
Dale L
DL
Burt
David S
DS
Lowell
George H
GH
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D003546:Cysteine Endopeptidases / Q000008:administration & dosage* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004338:Drug Combinations; D005260:Female; D007114:Immunization; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D064370:Spike Glycoprotein, Coronavirus; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000914:Antibodies, Viral; D016207:Cytokines; D004338:Drug Combinations; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C493785:Protollin; D064370:Spike Glycoprotein, Coronavirus; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D003546:Cysteine Endopeptidases