title: Intranasal immunization with an archaeal lipid mucosal vaccine adjuvant and delivery formulation protects against a respiratory pathogen challenge.
abstract: Archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) is a safe mucosal adjuvant that elicits long lasting and memory boostable mucosal and systemic immune responses to model antigens such as ovalbumin. In this study, we evaluated the potential of the AMVAD system for eliciting protective immunity against mucosal bacterial infections, using a mouse model of intranasal Francisella tularensis LVS (LVS) challenge. Intranasal immunization of mice with cell free extract of LVS (LVSCE) adjuvanted with the AMVAD system (LVSCE/AMVAD) induced F. tularensis-specific antibody responses in sera and bronchoalveolar lavage fluids, as well as antigen-specific splenocyte proliferation and IL-17 production. More importantly, the AMVAD vaccine partially protected the mice against a lethal intranasal challenge with LVS. Compared to LVSCE immunized and naïve mice, the LVSCE/AMVAD immunized mice showed substantial to significant reduction in pathogen burdens in the lungs and spleens, reduced serum and pulmonary levels of proinflammatory cytokines/chemokines, and longer mean time to death as well as significantly higher survival rates (p<0.05). These results suggest that the AMVAD system is a promising mucosal adjuvant and vaccine delivery technology, and should be explored further for its applications in combating mucosal infectious diseases.
authors.affiliation: Institute for Biological Sciences, National Research Council Canada, Ottawa, Canada. girish.patel@nrc-cnrc.gc.ca
authors.forename: Girishchandra B
authors.initials: GB
authors.lastname: Patel
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.forename: Amalia
authors.initials: A
authors.lastname: Ponce
authors.forename: Greg
authors.initials: G
authors.lastname: Harris
authors.forename: Wangxue
authors.initials: W
authors.lastname: Chen
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D002474:Cell-Free System; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005604:Francisella tularensis / Q000378:metabolism; D006801:Humans; D007114:Immunization / Q000379:methods*; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D009092:Mucous Membrane / Q000382:microbiology; D010047:Ovalbumin / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000382:microbiology*; D014018:Tissue Distribution
chemical_list: D000942:Antigens, Bacterial; D018925:Chemokines; D016207:Cytokines; D020381:Interleukin-17; D010047:Ovalbumin