Herpes simplex virus nanoemulsion vaccine
Inventors
Fattom, Ali I. • Simon, Jakub • Baker, Jr., James R. • Hamouda, Tarek • Bitko, Vira
Assignees
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Publication Number
US-10206996-B2
Publication Date
2019-02-19
Expiration Date
Abstract
The present application relates to the field of human immunology, in particular, a herpes simplex virus (HSV) vaccine. The subunit vaccine composition comprises isolated surface glycoproteins from herpes simplex viruses, fusion proteins or fragments thereof mixed in varied combination with a nanoemulsion, which is a potent immune enhancer.
Core Innovation
The disclosed invention relates to a mucosal herpes simplex virus (HSV) vaccine concept in which HSV antigens are combined with an immune enhancing oil-in-water nanoemulsion suitable for mucosal administration. The vaccine includes droplets having an average diameter less than about 600 nm and includes an aqueous phase together with a defined pharmaceutically acceptable oil, surfactants, an organic solvent selected as an alcohol, and a cationic surfactant. The combination is used to induce broad humoral and cellular immunity after mucosal delivery.
The invention further centers on including a combination of isolated HSV gD antigen and isolated HSV gB antigen within the nanoemulsion. The HSV gD antigen is described as an HSV-1 gD, HSV-2 gD, or an immunogenic fragment of HSV-1 gD or HSV-2 gD, and the HSV gB antigen is described as an HSV-1 gB, HSV-2 gB, or an immunogenic fragment of HSV-1 gB or HSV-2 gB. Documented compositions also include an HSV mucosal subunit vaccine composition consisting essentially of an immune enhancing nanoemulsion and multivalent HSV gD and multivalent HSV gB antigens, with the nanoemulsion diluted to about 20% in an aqueous phase to make it suitable for mucosal administration.
In addition, the disclosed material describes preparing recombinant full length or immunogenic fragment HSV antigens in a eukaryotic host and isolating the antigens prior to formulating the combination with the oil-in-water nanoemulsion. Supporting observations described in the content indicate antigen localization in the droplet oil core, supported by TEM observations. The document also describes mucosal immune outcomes including neutralizing antibodies and mucosal immunity, including IgA, and immune response profiles comprising Th1, Th2 and/or Th17, with utility discussed against drug-resistant HSV strains and delivery routes including intranasal and intravaginal administration.
Claims Coverage
The provided claim set includes three independent claims: a mucosal HSV vaccine composition, a method for preparing a mucosal HSV vaccine, and an HSV mucosal subunit vaccine composition. Across these independent claims, the main inventive features are the combination of gD and gB antigens with a specifically defined mucosal-suitable oil-in-water nanoemulsion, recombinant antigen synthesis in a eukaryotic host, and subunit/vaccine formulation for mucosal administration with defined dilution.
Mucosal HSV vaccine composition with immune enhancing nanoemulsion and isolated gD and gB antigens
A mucosal herpes simplex virus (HSV) vaccine composition consisting essentially of an immune enhancing nanoemulsion suitable for mucosal administration comprising droplets having an average diameter less than about 600 nm, an aqueous phase, about 12.6% of a pharmaceutically acceptable oil, about 1.18% of at least one surfactant selected from Polysorbate 80, Polysorbate 20, or a combination thereof, about 1.35% of at least one organic solvent where the organic solvent is an alcohol, and about 0.2% of a cationic surfactant where the cationic surfactant is cetylpyridinium chloride (CPC) or dioctyl dimethyl ammonium chloride; and a combination comprising an isolated HSV gD antigen and an isolated HSV gB antigen within the nanoemulsion, where HSV gD is HSV-1 gD, HSV-2 gD, or an immunogenic fragment of HSV-1 gD or HSV-2 gD, and HSV gB is HSV-1 gB, HSV-2 gB, or an immunogenic fragment of HSV-1 gB or HSV-2 gB.
Method of preparing mucosal HSV vaccine via eukaryotic recombinant antigen synthesis and nanoemulsion formulation
A method for preparing a mucosal herpes simplex virus (HSV) vaccine useful for the treatment or prevention of an HSV infection in humans comprising synthesizing in a eukaryotic host one or more recombinant, full length or immunogenic fragment HSV antigens selected from HSV-1 gB, HSV-2 gB, HSV-1 gD, and HSV-2 gD; isolating the one or more antigens or immunogenic fragments thereof from the eukaryotic host; and formulating a combination comprising an isolated HSV gD antigen and an isolated HSV gB antigen with an oil-in-water nanoemulsion, where the nanoemulsion or a dilution thereof comprises droplets having an average diameter less than about 600 nm, an aqueous phase, about 63% of a pharmaceutically acceptable oil, about 5.9% of at least one surfactant selected from Polysorbate 80 and Polysorbate 20 or a combination thereof, about 6.75% of at least one organic solvent where the organic solvent is an alcohol, and about 1% of a cationic surfactant.
HSV mucosal subunit vaccine composition with diluted immune enhancing nanoemulsion and multivalent gD and gB antigens
A herpes simplex virus (HSV) mucosal subunit vaccine composition consisting essentially of an immune enhancing nanoemulsion comprising droplets having an average diameter less than about 600 nm, an aqueous phase, about 63% of a pharmaceutically acceptable oil, about 5.9% of at least one surfactant selected from Polysorbate 80 and Polysorbate 20 or a combination thereof, about 6.75% of at least one organic solvent where the organic solvent is an alcohol, and about 1.0% of a cationic surfactant where the cationic surfactant is cetylpyridinium chloride (CPC) or dioctyl dimethyl ammonium chloride; and a combination comprising an isolated multivalent HSV gD antigen and an isolated multivalent HSV gB antigen within the nanoemulsion, where HSV gD is HSV-1 gD, HSV-2 gD, or an immunogenic fragment of HSV-1 gD or HSV-2 gD, and HSV gB is HSV-1 gB, HSV-2 gB, or an immunogenic fragment of HSV-1 gB or HSV-2 gB, wherein the immune enhancing nanoemulsion is diluted to about 20% in an aqueous phase thereby making it suitable for mucosal administration.
Across the independent claims, coverage focuses on mucosal HSV vaccination by combining isolated HSV gD and isolated HSV gB antigens with a defined immune enhancing oil-in-water nanoemulsion characterized by droplets less than about 600 nm and specific oil, surfactant, solvent, and cationic surfactant components. The method claim additionally specifies generating recombinant full length or immunogenic fragment HSV antigens in a eukaryotic host and then formulating the isolated gD and gB antigens with the nanoemulsion.
Stated Advantages
Induces broad humoral and cellular immunity after mucosal delivery.
Induces neutralizing antibodies.
Induces mucosal immunity including IgA.
Induces immune response profiles comprising Th1, Th2 and/or Th17.
Utility discussed against drug-resistant HSV strains.
Documented Applications
Treatment or prevention of HSV infection in humans using a mucosal HSV vaccine prepared by the claimed method.
Mucosal administration including intranasal administration and intravaginal administration of the HSV vaccine compositions.
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