Liposomal vaccine adjuvants and methods of making and using same
Inventors
Sorayya, Aryo • Mosharraf, Mitra • Nayar, Rajiv
Assignees
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Publication Number
US-9603799-B2
Publication Date
2017-03-28
Expiration Date
Abstract
A vaccine adjuvant composition comprising: a lipid selected from the group consisting of: dipalmitoyl phosphatidlcholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG), dioleoyl phosphatidylcholine (DOPC), and cholesterol and containing a positively or negatively charged lipid with associated/entrapped protein antigen.
Core Innovation
The invention relates to liposome-associated antigen compositions that are injectable and immunogenic. The liposomes comprise DPPC, DOPC, cholesterol and stearylamine (SA), with a specified DPPC:DOPC:cholesterol:positively charged lipid molar ratio. The antigen is entrapped within the aqueous compartment of the liposome, entrapped within the lipid bilayer, and/or adsorbed to the liposomal surface.
The antigen includes at least one member selected from polynucleotides, polypeptides, recombinant proteins, synthetic peptides, and protein extract isolated from pathogens. The pathogens identified include Corynebacterium diphtheria, Bordetella pertussis, influenza virus, hepatitis B virus, Clostridium botulinum, and Bacillus anthracis. The composition further includes lysozyme.
The disclosure emphasizes freeze stability and lyophilized, freeze-compatible formulations. The compositions retain immunogenicity after freeze-drying/freezing and are described as freeze stable through multiple freeze-thaws and low-temperature lyophilization, with particle size stability including for lyophilized formulations.
The compositions are described as liposomal vaccine adjuvant compositions with lysozyme and liposome-associated protein antigens, including lysozyme and tetanus light chain (TLC). The disclosure contrasts performance against aluminum-phosphate adjuvant controls and describes formulations that omit certain co-adjuvants while retaining immunogenicity.
Claims Coverage
The independent claim is clm-00001. It contains four main inventive features: a specific liposome lipid composition and molar ratio, liposome-associated antigen positioning, defined antigen categories including selected pathogen protein extracts, and inclusion of lysozyme in an injectable immunogenic composition.
Liposome composition with defined molar ratio
An injectable immunogenic composition where the liposomes comprise DPPC, DOPC, cholesterol and stearylamine (SA) with a DPPC:DOPC:cholesterol:positively charged lipid molar ratio of 40:20-30:20:10-20.
Liposome-associated antigen with aqueous/lipid entrapment and/or surface adsorption
The antigen is entrapped within the aqueous compartment of the liposome, entrapped within the lipid bilayer, and/or adsorbed to the liposomal surface.
Antigen selection including pathogen protein extract categories
The antigen is at least one member selected from polynucleotides, polypeptides, recombinant proteins, synthetic peptides and protein extract isolated from pathogens selected from Corynebacterium diphtheria, Bordetella pertussis, influenza virus, hepatitis B virus, Clostridium botulinum, and Bacillus anthracis.
Injectable composition includes lysozyme
The injectable immunogenic composition further includes lysozyme.
Across the independent claim, the inventive coverage centers on an injectable immunogenic composition using a DPPC/DOPC/cholesterol/SA liposome with a defined molar ratio, where a selected category of antigens is entrapped in aqueous and/or lipid compartments and/or adsorbed to the surface, and where lysozyme is included.
Stated Advantages
Freeze stability, including retained immunogenicity after freeze-drying/freezing and multiple freeze-thaws.
Comparative or improved antibody responses versus aluminum-phosphate adjuvant controls, as described in the disclosure.
Safety/tolerability advantages over aluminum-based adjuvants are discussed in the disclosure.
Particle size stability, including for lyophilized formulations, with mean hydrodynamic particle diameter in the stated range.
Documented Applications
Immunogenic compositions for injectable vaccination use are described, including mouse immunogenicity examples using lysozyme and tetanus light chain (TLC) antigens.
Vaccine adjuvant compositions are described for antigens including protein antigens associated with pathogens selected from Corynebacterium diphtheria, Bordetella pertussis, influenza virus, hepatitis B virus, Clostridium botulinum, and Bacillus anthracis.
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