Herpes simplex virus nanoemulsion vaccines and methods of using the same

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.

1 . A vaccine composition comprising:
 (a) an immune enhancing nanoemulsion, wherein the nanoemulsion comprises an oil-in-water nanoemulsion or a dilution thereof; and   (b) at least one herpes simplex virus (HSV) antigen, wherein the HSV antigen is whole HSV virus, an isolated HSV antigen, or a combination thereof, and wherein the HSV antigen is present within the nanoemulsion.   
     
     
         2 . The vaccine composition of  claim 1 , wherein the HSV antigen is inactivated prior to incorporation into a nanoemulsion and/or where the HSV antigen is inactivated by the nanoemulsion. 
     
     
         3 . The vaccine composition of  claim 1 , wherein the HSV antigen is an HSV surface antigen derived from HSV and comprising at least one antigen selected from the group consisting of:
 (a) an isolated HSV gB glycoprotein or an immunogenic fragment thereof,   (b) an isolated HSV gC glycoprotein or an immunogenic fragment thereof,   (c) an isolated HSV gD glycoprotein or an immunogenic fragment thereof, or   (d) an isolated HSV gE glycoprotein or an immunogenic fragment thereof.   
     
     
         4 . The vaccine composition of  claim 3 , wherein one or more HSV surface antigens further comprise nucleotide modifications denoting attenuating phenotypes. 
     
     
         5 . The vaccine composition of  claim 3 , wherein at least one HSV surface antigen is present in a fusion protein. 
     
     
         6 . The vaccine composition of  claim 3 , wherein at least one HSV surface antigen is present in an immunogenic peptide fragment of HSV gB, HSV gC, HSV gD or HSV gE glycoprotein or an immunogenic derivative thereof. 
     
     
         7 . The vaccine composition of  claim 1 , wherein the immune enhancing nanoemulsion is capable of inducing Th1, Th2 and/or Th17 immune responses. 
     
     
         8 . The vaccine composition of  claim 1 , wherein the nanoemulsion particle size is from about 300 nm up to about 600 nm. 
     
     
         9 . The vaccine composition of  claim 1  additionally comprising an adjuvant. 
     
     
         10 . The vaccine composition of  claim 1  further comprising a pharmaceutically acceptable carrier. 
     
     
         11 . The vaccine composition of  claim 1 , wherein the vaccine composition is administered either parenterally, intravaginally, orally or intranasally. 
     
     
         12 . The vaccine composition of  claim 11 , wherein the parenteral administration is by subcutaneous, intraperitoneal or intramuscular injection. 
     
     
         13 . A method for inducing an enhanced immunity against diseases caused by herpes simplex viruses comprising the step of administering to an individual an effective amount of a nanoemulsion HSV vaccine composition comprising:
 (a) a nanoemulsion, wherein the nanoemulsion comprises an oil-in-water nanoemulsion or a dilution thereof; and   (b) at least one herpes simplex virus (HSV) antigen, wherein the HSV antigen is whole HSV virus, an isolated HSV antigen, or a combination thereof, and wherein the at least one HSV antigen is present within the nanoemulsion.   
     
     
         14 . The method of  claim 13 , wherein the HSV antigen is an HSV surface antigen derived from HSV and comprising at least one isolated HSV gB, HSV gC, HSV gD or HSV gE glycoproteins or an immunogenic fragment thereof 
     
     
         15 . The method of  claim 13 , wherein the step of administering comprises parenterally, intravaginally, orally or intranasally. 
     
     
         16 . A method for preparing a nanoemulsion HSV vaccine useful for the treatment or prevention of an HSV infection in humans comprising:
 (a) synthesizing in a eukaryotic host one or more full length or immunogenic fragment HSV surface antigens utilizing recombinant DNA genetics vectors and constructs, wherein the HSV surface antigen is selected from the group consisting of HSV gB, HSV gC, HSV gD, and HSV gE;   (b) isolating the one or more surface antigens or immunogenic fragments thereof from the eukaryotic host; and   (c) formulating the one or more surface antigens with an oil-in-water nanoemulsion.   
     
     
         17 . The method according to  claim 16 , wherein the eukaryotic host is a mammalian cell or a yeast cell. 
     
     
         18 . (canceled) 
     
     
         19 . The method according to  claim 16 , wherein the HSV is HSV-1 or HSV-2. 
     
     
         20 - 26 . (canceled) 
     
     
         27 . The vaccine composition of  claim 1 , wherein the oil-in-water nanoemulsion comprises
 (a) droplets having an average diameter of less than about 1000 nm;   (b) an aqueous phase;   (c) about 1% to about 80% of a pharmaceutically acceptable oil;   (d) about 0.001% to about 10% of at least one surfactant, wherein the surfactant is Polysorbate 80, Polysorbate 20, or a combination thereof;   (e) about 0.1% to about 50% of at least one organic solvent, wherein the organic solvent is an alcohol; and   (f) greater than 0.001% and less than about 5% of a cationic surfactant.   
     
     
         28 . The vaccine composition of  claim 27 , wherein the cationic surfactant is cetylpyridinium chloride or dioctyl dimethyl ammonium chloride. 
     
     
         29 . The vaccine composition of  claim 27 , wherein the pharmaceutically acceptable oil is selected from the group consisting of mineral oil, squalene oil, flavor oils, silicon oil, essential oils, water insoluble vitamins, Isopropyl stearate, Butyl stearate, Octyl palmitate, Cetyl palmitate, Tridecyl behenate, Diisopropyl adipate, Dioctyl sebacate, Menthyl anthranhilate, Cetyl octanoate, Octyl salicylate, Isopropyl myristate, neopentyl glycol dicarpate cetols, Ceraphyls®, Decyl oleate, diisopropyl adipate, C 12-15  alkyl lactates, Cetyl lactate, Lauryl lactate, Isostearyl neopentanoate, Myristyl lactate, Isocetyl stearoyl stearate, Octyldodecyl stearoyl stearate, Hydrocarbon oils, Isoparaffin, Fluid paraffins, Isododecane, Petrolatum, Argan oil, Canola oil, Chile oil, Coconut oil, corn oil, Cottonseed oil, Flaxseed oil, Grape seed oil, Mustard oil, Olive oil, Palm oil, Palm kernel oil, Peanut oil, Pine seed oil, Poppy seed oil, Pumpkin seed oil, Rice bran oil, Safflower oil, Tea oil, Truffle oil, Vegetable oil, Apricot (kernel) oil, Jojoba oil (simmondsia chinensis seed oil), Grapeseed oil, Macadamia oil, Wheat germ oil, Almond oil, Rapeseed oil, Gourd oil, Soybean oil, Sesame oil, Hazelnut oil, Maize oil, Sunflower oil, Hemp oil, Bois oil, Kuki nut oil, Avocado oil, Walnut oil, Fish oil, berry oil, allspice oil, juniper oil, seed oil, almond seed oil, anise seed oil, celery seed oil, cumin seed oil, nutmeg seed oil, leaf oil, basil leaf oil, bay leaf oil, cinnamon leaf oil, common sage leaf oil, eucalyptus leaf oil, lemon grass leaf oil, melaleuca leaf oil, oregano leaf oil, patchouli leaf oil, peppermint leaf oil, pine needle oil, rosemary leaf oil, spearmint leaf oil, tea tree leaf oil, thyme leaf oil, wintergreen leaf oil, flower oil, chamomile oil, clary sage oil, clove oil, geranium flower oil, hyssop flower oil, jasmine flower oil, lavender flower oil, manuka flower oil, Marhoram flower oil, orange flower oil, rose flower oil, ylang-ylang flower oil, Bark oil, cassia Bark oil, cinnamon bark oil, sassafras Bark oil, Wood oil, camphor wood oil, cedar wood oil, rosewood oil, sandalwood oil), rhizome (ginger) wood oil, resin oil, frankincense oil, myrrh oil, peel oil, bergamot peel oil, grapefruit peel oil, lemon peel oil, lime peel oil, orange peel oil, tangerine peel oil, root oil, valerian oil, Oleic acid, Linoleic acid, Oleyl alcohol, Isostearyl alcohol, semi-synthetic derivatives thereof, and any combinations thereof. 
     
     
         30 . The vaccine composition of  claim 27 , wherein the alcohol is a C 1 -C 12  alcohol. 
     
     
         31 . The vaccine composition of  claim 30 , wherein the C 1 -C 12  alcohol is ethanol.