Intranasal Immunization with an Archaeal Lipid Mucosal Vaccine Adjuvant and Delivery Formulation Protects against a Respiratory Pathogen Challenge

Girishchandra B Patel,Amalia Ponce,Hongyan Zhou,Wangxue Chen,Greg Harris,T Mark Doherty

doi:10.1371/journal.pone.0015574

Girishchandra B Patel, Amalia Ponce + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0015574

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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.

Highlights

Many microbial pathogens invade their human and animal hosts through the mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts [1,2]
The anti-LVS cell free extract (LVSCE) IgA antibody titres measured in the sera and bronchoalveolar lavage (BAL) fluids of mice immunized with the LVSCE/AMVAD vaccine were strong and much higher than those seen with LVSCE alone immunization or in naıve mice (Fig. 1)
The systemic immune responses assessed as anti-LVSCE IgM and IgG1 antibody titres in sera from mice immunized with LVSCE/AMVAD and LVSCE/cholera toxin (CT) vaccines were strong, and generally comparable (Fig. 2)

Summary

Introduction

Many microbial pathogens invade their human and animal hosts through the mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts [1,2]. The few mucosal vaccines currently in the marketplace are all based on the use of live-attenuated or dead pathogen cells [3,5,6,7]. Vaccines based on acellular or subunit antigens would be safer, but such antigens are generally poorly immunogenic on their own [3,10,11] This has sustained global research efforts at developing mucosal adjuvants and nonreplicating delivery systems such as detoxified cholera toxin (CT) and Escherichia coli heat labile toxin, CpG oligonucleotides, DNA, microparticulates such as virosomes, liposomes, cochleates, polymeric microspheres, and immunostimulating complexes such as ISCOMs [8,9,11,12]

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