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.

Selection of Adjuvants for Enhanced Vaccine Potency

“…Many other lipids have been shown to have immunomodulating effect, certainly for those from microorganisms [308,309]. Lysophosphatidylcholine (LPC) mixed with various antigens induced cytotoxic T cell responses and production of antigen-specific antibodies with an efficiency similar to Alum in mice [310].…”

Leaf-Encapsulated Vaccines: Agroinfiltration and Transient Expression of the AntigenStaphylococcal EndotoxinB in Radish Leaves

“…The functionality of SEB-GUS encapsulated in radish leaves as a vaccine was tested. Without purifying SEB from leaves, whole leaves infiltrated with A. tumefaciens carrying a 35S:: SEB - GUS (L-SEB-GUS) or a 35S:: GUS (L-GUS) construct were ground in sterile water, ultraviolet-inactivated, and mixed with cholera toxin, a common adjuvant used for intranasal immunization [ 50 ]. The ground leaves were subsequently inoculated into nasal cavities of ICR mice for intranasal immunization.…”

Sulfated archaeal glycolipid archaeosomes as a safe and effective vaccine adjuvant for induction of cell-mediated immunity

“… 8, 15 While typically administered by systemic routes such as subcutaneous or intramuscular injection, the formulation of archaeol TPLs with cations results in the formation of aggregated structures termed archaeal mucosal adjuvant delivery system (AMVAD) which is suitable for mucosal delivery via intranasal routes. 16, 17, 18 The effectiveness of the AMVAD system was demonstrated by the induction of strong antigen-specific immune responses and protection against bacterial infection using a murine model of intranasal Francisella tularensis LVS (LVS) challenge to mice immunized intranasally with cell free extract of LVS adjuvanted with the AMVAD system. 16 Furthermore, the addition of a detergent, sodium cholate, to TPL archaeosomes has been shown to generate ultradeformable archaeosomes (UDA) for topical delivery of vaccines to the skin.…”

“… 16, 17, 18 The effectiveness of the AMVAD system was demonstrated by the induction of strong antigen-specific immune responses and protection against bacterial infection using a murine model of intranasal Francisella tularensis LVS (LVS) challenge to mice immunized intranasally with cell free extract of LVS adjuvanted with the AMVAD system. 16 Furthermore, the addition of a detergent, sodium cholate, to TPL archaeosomes has been shown to generate ultradeformable archaeosomes (UDA) for topical delivery of vaccines to the skin. 19, 20 Nevertheless, despite these successes, the TPL archaeosome formulations typically used are relatively complex and comprise multiple lipid species.…”