Targeting of nasal mucosa-associated antigen-presenting cells in vivo with an outer membrane protein A derived from Klebsiella pneumoniae.
Administration of vaccines by the nasal route has recently proven to be one of the most efficient ways for inducing both mucosal and systemic antibody responses in experimental animals. Our results demonstrate that P40, a well-defined outer membrane protein A from Klebsiella pneumoniae, is indeed a carrier molecule suitable for nasal immunization. Using fragments from the respiratory syncytial virus subgroup A (RSV-A) G protein as antigen models, it has been shown that P40 is able to induce both systemic and mucosal immunity when fused or coupled to a protein or a peptide and administered intranasally (i.n.) to naive or K. pneumoniae-primed mice. Confocal analyses of nasal mucosa-associated lymphoid tissue after i.n. instillation of P40 showed that this molecule is able to cross the nasal epithelium and target CD11c-positive cells likely to be murine dendritic cells or macrophages. More importantly, this targeting of antigen-presenting cells following i.n. immunization with a subunit of the RSV-A molecule in the absence of any mucosal adjuvant results in both upper and lower respiratory tract protection against RSV-A infection.
Goetsch
L
L
Centre d'Immunologie Pierre Fabre, 74164 Saint-Julien en Genevois, France. liliane.goetsch@pierre-fabre.com
Gonzalez
A
A
Plotnicky-Gilquin
H
H
Haeuw
J F
JF
Aubry
J P
JP
Beck
A
A
Bonnefoy
J Y
JY
Corvaïa
N
N
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D000956:Antigens, Viral; D001425:Bacterial Outer Membrane Proteins; D011993:Recombinant Fusion Proteins; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C078167:OMPA outer membrane proteins