Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge

Abstract

We have previously shown that following intranasal exposure to influenza virus, specific plasma cells are generated in the nasal-associated lymphoid tissue (NALT) and maintained for the life of the animal. However, we also showed that following infection with respiratory syncytial virus (RSV), specific plasma cells are generated in the NALT but wane quickly and are not maintained even after challenge, even though RSVspecific serum antibody responses remain robust. Only infection with influenza virus generated sterilising immunity, implying a role for these long-lived plasma cells in protection. We show here that the RSV-specific IgA NALT plasma cell population and lung antibody levels can be substantially boosted, both at acute and memory time points, by intranasal immunisation with inactivated RSV (iRSV) in combination with bacterial outer membrane vesicles (OMV) compared to live RSV alone. Finally, challenge with live RSV showed that immunisation with iRSV and OMV protect against both virus replication in the lung and the eosinophil infiltrate generated by either live RSV or iRSV alone. These data show that immunisation with iRSV and OMV maintains a NALT RSV-specific plasma cell population and generates an efficient protective immune response following RSV infection.See accompanying commentary: http://dx

Single Intranasal Immunization with Recombinant Adenovirus-Based Vaccine Induces Protective Immunity against Respiratory Syncytial Virus Infection

“…2A and B and 5A). These results are consistent with previous reports that stimulation and maintenance of local mucosal antibody may be important in the generation of effective protection (12,34). Since the infection route for RSV is via the respiratory tract, mucosal delivery might be critical for the development of protective immunity at the site of infection.…”

CXCR6 Is a Marker for Protective Antigen-Specific Cells in the Lungs after Intranasal Immunization against Mycobacterium tuberculosis

“…Here we targeted the NALT with Ad85A and CT in a small-volume inoculum (5 l) with the aim of ensuring a powerful NALT response (12). Even with the addition of CT, no CXCR6 ϩ cells were detected in the lung, although some were present in the NALT (data not shown).…”

“…of Ad85A. Mice were also immunized with recombinant antigen 85A protein (rec85A) or with a peptide carrying the first 20 amino acids of ESAT6 (6-kDa early secreted antigenic target; ESAT6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] ). Intranasal protein immunization was conducted as described above, delivering 2 g of rec85A protein or 20 g of ESAT6 1-20 mixed with 2 g of cholera toxin (CT; Sigma-Aldrich, Dorset, United Kingdom) into the nostrils in a 50-l volume.…”

Nasal Immunity to Staphylococcal Toxic Shock Is Controlled by the Nasopharynx-Associated Lymphoid Tissue

“…This process in turn drives expression of PNA receptors on B cells, characteristic of dark zones within the germinal center (6,26,45). Stimulation of NALT is characterized by the preferential secretion of soluble IgA, but also of IgG2 and IgG1 (11,28,38). It has been shown that in mice the NALT is the site of Ig isotype selection and generation of long-term immunity (28,39).…”