Intranasal vaccination with recombinant outer membrane protein CD and adamantylamide dipeptide as the mucosal adjuvant enhances pulmonary clearance of Moraxella catarrhalis in an experimental murine model.
Moraxella catarrhalis causes acute otitis media in children and lower respiratory tract infections in adults and elderly. In children the presence of antibodies against the highly conserved outer membrane protein CD correlates with protection against infection, suggesting that this protein may be useful as a vaccine antigen. However, native CD is difficult to purify, and it is still unclear if recombinant CD (rCD) is a valid alternative. We performed a side-by-side comparison of the immunogenicities and efficacies of vaccine formulations containing native CD and rCD with adamantylamide dipeptide as the mucosal adjuvant. Intranasal vaccination of mice stimulated the production of high CD-specific antibody titers in sera and of secretory immunoglobulin A in mucosal lavages, which cross-recognized both antigens. While vaccination with native CD increased the number of interleukin-2 (IL-2)- and gamma interferon-producing cells, rCD mainly stimulated IL-4-secreting cells. Nevertheless, efficient bacterial clearance was observed in the lungs of challenged mice receiving native CD and in the lungs of challenged mice receiving rCD (96% and 99%, respectively). Thus, rCD is a promising candidate for incorporation in vaccine formulations for use against M. catarrhalis.
Becker
Pablo D
PD
Virology Laboratory, Ricardo Gutiérrez Children's Hospital, Gallo 1330, 1425 Buenos Aires, Argentina.
Bertot
Gustavo M
GM
Souss
David
D
Ebensen
Thomas
T
Guzmán
Carlos A
CA
Grinstein
Saúl
S
D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000547:Amantadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D049109:Cell Proliferation; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004151:Dipeptides / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000276:immunology* / Q000302:isolation & purification; D045828:Moraxellaceae Infections / Q000276:immunology* / Q000382:microbiology; D009092:Mucous Membrane / Q000276:immunology; D013154:Spleen / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D004151:Dipeptides; D007071:Immunoglobulin A, Secretory; D007378:Interleukins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C484698:outer membrane protein CD, Moraxella catarrhalis; D007371:Interferon-gamma; C044891:adamantylamide-alanyl-isoglutamine; D000547:Amantadine