Targeting of nasal mucosa-associated antigen-presenting cells in vivo withan 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 wel l-defined outer membrane protein A from Klesiella pneumoniae, is indeed a c arrier molecule suitable for nasal immunization. Using fragments from the r espiratory 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 immu nity when fused or coupled to a protein or a peptide and administered intra nasally (i.n.) to naive or K. pneumoniae-primed mice. Confocal analyses of nasal mucosa-associated lymphoid tissue after i.n. instillation of P40 show ed that this molecule is able to cross the nasal epithelium and target CD11 c-positive cells likely to be murine dendritic cells or macrophages. More i mportantly, this targeting of antigen-presenting cells following i.n. immun ization with a subunit of the RSV-A molecule in the absence of any mucosal adjuvant results in both upper and lower respiratory tract protection again st RSV-A infection.