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Novel adjuvants derived from attenuated lipopolysaccharides and lipid As of purple non-sulfur photosynthetic bacteria |
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| Institution: | 1. Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany;2. Berlin-Brandenburg, Center of Regenerative Therapies (BCRT), Berlin, Germany;3. Berlin Institute of Health (BIH), Charité and Max-Delbrück Center, Berlin, Germany |
| Abstract: | Adjuvants are substances that enhance adaptive immune response to antigen. Development of a safe and effective immunostimulant adjuvant is essential for the efficacy of a vaccine to protect against infectious pathogens. Purple non-sulfur photosynthetic bacteria exhibited nontoxic natural lipid A variants that are distinct in their chemical structures from that of the Escherichia coli-type lipid A. In this study, the adjuvant efficacy of attenuated lipid A variants and their corresponding lipopolysaccharides (LPSs), derived from purple photosynthetic bacteria (Rhodocyclus tenuis and Rhodobacter sphaeroides) were evaluated. LPS was extracted using modified phenol-chloroform-petroleum ether method and lipid A was separated by mild acid hydrolysis. Trinitrophenol (TNP) was conjugated to hen egg albumin (TNP-HEA) and used as haptenic antigen. The LPS and lipid A adjuvant candidates were formulated in oil-in-water emulsion (OIWE) and evaluated to elicit anti-TNP IgG against TNP-HEA conjugate in BALB/c female mice. The anti-TNP IgG titers were measured using ELISA. The intact LPS-based adjuvants present in OIWE formulation showed significantly higher efficacy to elicit anti-TNP IgG titers against TNP-HEA conjugate compared to their corresponding lipid A-based adjuvants. As expected, the OIWE formulations of all LPS- and lipid A-based adjuvant candidates showed higher activities compared to the aqueous formulations. Slow reduction in the levels of anti-TNP IgG antibodies in the serum was observed over 4 months after immunization using the LPS- and lipid A-based adjuvant candidates which may provide a long protection against pathogens. The attenuated LPSs and lipid A’s from the photosynthetic bacteria showed promising results to develop novel safe and effective adjuvants that can evoke the immune response. The most promising adjuvant candidate was the LPS-based adjuvant from R. tenuis. |
| Keywords: | Adjuvant Lipid A LPS Oil-in-water emulsion Kdo"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"2-keto-3-deoxyoctylosonic acid LPS"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"lipopolysaccharide OS"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"oligosaccharide MPL"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"monophosphoryl lipid A DSMZ"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"Deutsche Sammlung von Mikroorganismen und Zellkulturen FA"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"Freund’s adjuvant CFA"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"complete Freund’s adjuvant AS"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"adjuvant systems PCP"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"phenol-chloroform-petroleum ether ELISA"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"enzyme linked immunosorbant assay TDM"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"trehalose dicorynomycolate S-TDCM"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"synthetic trehalose dicorynomycolate TNBS"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"2 3 4-trinitrobenzenesulfonic acid TNP"} {"#name":"keyword" "$":{"id":"k0170"} "$$":[{"#name":"text" "_":"trinitrophenol HEA"} {"#name":"keyword" "$":{"id":"k0180"} "$$":[{"#name":"text" "_":"hen egg albumin BSA"} {"#name":"keyword" "$":{"id":"k0190"} "$$":[{"#name":"text" "_":"bovine serum albumin TNP-HEA"} {"#name":"keyword" "$":{"id":"k0200"} "$$":[{"#name":"text" "_":"trinitrophenol-hen egg albumin conjugate TNP-BSA"} {"#name":"keyword" "$":{"id":"k0210"} "$$":[{"#name":"text" "_":"trinitrophenol-bovine serum albumin conjugate PBS"} {"#name":"keyword" "$":{"id":"k0220"} "$$":[{"#name":"text" "_":"phosphate buffered saline OIWE"} {"#name":"keyword" "$":{"id":"k0230"} "$$":[{"#name":"text" "_":"oil in water emulsion BBS"} {"#name":"keyword" "$":{"id":"k0240"} "$$":[{"#name":"text" "_":"borate buffer saline |
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