Vaccine 2013 Nov;31(48):5729-5735.

Intranasal immunization with a non-adjuvanted adhesive protein descended from Pasteurella pneumotropica and its preventive efficacy against opportunistic infection in mice. 

Sasaki H, Ishikawa H, Kojima K, Itoh M, Matsumoto T, Itoh T, Hosomi O, Kawamoto E

Correspondence: hirakus@juntendo.ac.jp

Abstract

Intranasal vaccination is one of the most effective means of protecting against invading and colonizing pathogens because the vaccine elicits a mucosal immune response. The exploitation of vaccine adjuvants and delivery systems for intranasal vaccines is an important way to evoke antigen immunogenicity and elicit a better immune response at the mucosal sites. In the present study, we assessed the potential of intranasal immunization using a non-adjuvanted bacterial adhesive protein toward the host organs. We evaluated intranasal immunization with modified recombinant PnxIIIA (MP3) from Pasteurella pneumotropica and its preventive efficacy against opportunistic infection caused by P. pneumotropica, without using any adjuvants or delivery systems. The 100-kDa MP3 was confirmed to retain its immunogenicity and binding activity to collagen type I similar to the parent PnxIIIA. When MP3 was fused to green-fluorescent protein and inoculated into C57BL/6J mice intranasally, fluorescence intensity in the intranasal airway could be observed until 3 h after inoculation. Mice were intranasally immunized with MP3 at a maximum of 4 doses, with 7-day intervals. The antibody titer of serum IgG and IgA specific for MP3, as well as that of bronchoalveolar lavage fluid IgA, showed more than 9 (log₂) after 3 or 4 rounds of immunization. Experimentally infecting immunized mice with P. pneumotropica resulted in the inability to isolate the bacterium from the nasal cavity, trachea, conjunctiva, or cecum with more than 3 doses in the immunized mice. Although the detection in each organ seldom changed with less than 2 rounds of immunization, unlike that observed in the non-immunized mice, the detection remarkably decreased with 3 or more rounds of immunization. These results suggest that intranasal immunization with a non-adjuvanted adhesive protein could have preventive effects against opportunistic infection by P. pneumotropica.

PMID: 24091313

 

Supplement

     Intranasal vaccination is one of effective methods to elicit mucosal and systemic immune response.  In particular, IgA is known to be the most abundantly synthesized isotype, and secretory IgA (sIgA) is also known to defend mucosal surface against invasive pathogens.  To induce mucosal immune response, design of vaccine antigen and adjuvant required for intranasal vaccination is important issues.

     The study by Sasaki et al. demonstrated the intranasal immunization using collagen-binding protein, termed as PnxIIIA derived from rodent pathogen P. pneumotropica (Pp) in mice.  Although putative virulence associations are involved, the PnxIIIA was modified to less cytotoxicity protein MP3 with retaining its immunogenicity and collagen-binding activity.  Multiple MP3 intranasal vaccinations successfully prevented mice against opportunistic infection by Pp (Figure).  This study did not focus on only prevention of Pp infection in mice but broad perspective of mucosal immunization strategy.  In brief, MP3 itself is considered to act as a delivery protein, and therefore intranasal vaccination of MP3 combined with the other pathogen’s antigen may help elicit the pathogen-specific IgA production.  Further, non-adjuvanted pathogens’ adhesive proteins themselves with ability to bind epithelial surface have possibility to induce protective sIgA production even in opportunistic infection.
Figure

Figure 1. Schematic reprensentation of non-adjuvanted MP3 intranasal immunization by Sasaki et al. P. pneumotropica PnxIIIA protein was modified to adequate vaccine immunogen, MP3 protein, with retaining immunogenicity and collagen-binding activity.  Non-adjuvanted MP3 was then immunized via intranasal route and was retained in nasal meatus for 3 or more hours after intranasal immunization.  MP3 retantion was observed GFP section in panel of murine nasal airway.  Multiple MP3 intranasal immunization prevented Pp infection.

Reference

Sasaki H, Ishikawa H, Kojima K, Itoh M, Matsumoto T, Itoh T, Hosomi O, Kawamoto E. Intranasal immunization with a non-adjuvanted adhesive protein descended from Pasteurella pneumotropica and its preventive efficacy against opportunistic infection in mice. Vaccine. 2013 Nov;31(48):5729-5735.

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