Subunit vaccines for herpes viruses and methods of use
The present disclosure generally relates to vaccine compositions for Herpes Simplex Viruses (HSV) types 1 and/or 2. The vaccines comprise isolated antigens or glycoprotein subunits of the viruses, optionally with an adjuvant, such as a cationic liposome DNA complex (CLDC). Also the present disclosure contains methods of vaccinating a subject utilizing these compositions.
1. A composition of isolated Herpes Simplex Virus type 2 (HSV-2) antigens comprising:
i) an isolated glycoprotein B2 (gB2) fragment, wherein the fragment of gB2 consists of amino acid residues 31-726 or amino acid residues 31-727, wherein residue numbering begins at the starting methionine of gB2;
ii) an isolated glycoprotein H2 (gH2) fragment in a complex with glycoprotein L2 (gL2) or a fragment thereof, wherein the fragment of gH2 consists of amino acid residues 21-802, wherein residue numbering begins at the starting methionine of gH2, and wherein the gL2 or fragment thereof comprises the ectodomain of the full length protein; and
iii) an adjuvant, in an amount effective to enhance the immune response to said antigens of steps i) and ii), comprising a cationic liposome delivery vehicle and an isolated non-coding nucleic acid molecule.
2. The composition of claim 1 , further comprising an isolated glycoprotein D2 (gD2) fragment , wherein the fragment of gD2 consists of amino acid residues 1-285, wherein residue numbering begins at the starting methionine of gD2.
3. The composition of claim 1 , wherein the isolated non-coding nucleic acid molecule is selected from the group consisting of:
i) an isolated nucleic acid molecule that is not operatively linked to a transcription control sequence,
ii) an isolated bacterially-derived nucleic acid vector without a gene insert, and
iii) an oligonucleotide comprising a CpG motif.
4. The composition of claim 1 , wherein the cationic liposome delivery vehicle comprises one of the following combinations: N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP) and cholesterol; 1,2-di-O-octadecenyl-3-trimethylammonium propane chloride (DOTMA) and cholesterol; dimethyldioctadecylammonium bromide (DDAB) and cholesterol; or 1-[2-(9-(Z)-octadecenoyloxy)ethyl]-2-(8-(Z)-heptadecenyl)-3-(hydroxyethyl)imidazolinium chloride (DOTIM) and cholesterol.
5. A method for inducing an immune response in a mammalian subject against herpes simplex virus (HSV), comprising administering to the subject an effective amount of the composition of any of claims 1 , 2 , 3 , or 4 .
6. An isolated nucleic acid molecule consisting essentially of a nucleotide sequence encoding a HSV2 glycoprotein B2 (gB2) fragment, in-frame with a nucleotide sequence encoding a HSV2 glycoprotein H2 (gH2) fragment, and in-frame with a nucleotide sequence encoding HSV2 glycoprotein L2 (gL2) or a fragment thereof;
wherein the fragment of gB2 consists of amino acid residues 31-726 or amino acid residues 31-727, wherein residue number begins at the starting methionine of gB2;
wherein the fragment of gH2 consists of amino acid residues 21-802, wherein residue numbering begins at the starting methionine of gH2; and
wherein the gL2 or fragment thereof comprises the ectodomain of the full length protein.
7. An isolated nucleic acid molecule consisting essentially of a HSV2 nucleotide sequence encoding glycoprotein B2 (gB2) fragment, in-frame with a nucleotide sequence encoding a HSV2 glycoprotein H2 (gH2) fragment, in-frame with a nucleotide sequence encoding HSV2 glycoprotein L2 (gL2) or a fragment thereof, and in-frame with a nucleotide sequence encoding a HSV2 glycoprotein D2 (gD2) fragment;
wherein the fragment of gB2 consists of amino acid residues 31-726 or amino acid residues 31-727, wherein residue number begins at the starting methionine of gB2;
wherein the fragment of gH2 consists of amino acid residues 21-802, wherein residue numbering begins at the starting methionine of gH2; and
wherein the gL2 or fragment thereof comprises the ectodomain of the full length protein; and
wherein the fragment of gD2 consists of amino acid residues 1-285, wherein residue numbering begins at the starting methionine of gD2.
8. A composition comprising the isolated nucleic acid molecule of claim 6 .
9. A composition comprising the isolated nucleic acid molecule of claim 7 .
10. The composition of claim 8 or claim 9 , wherein the nucleic acids are complexed with a cationic liposome delivery vehicle to form a cationic liposome DNA complex (CLDC).
11. The composition of claim 10 , wherein the cationic liposome delivery vehicle comprises one of the following combinations: DOTAP and cholesterol; DOTMA and cholesterol; DDAB and cholesterol; or DOTIM and cholesterol.
12. A method for inducing an immune response in a mammalian subject against HSV-2, comprising concurrently or sequentially administering to the subject an effective amount of an isolated nucleic acid molecule according to claim 6 or 7 , wherein the nucleic acid molecule is complexed with a cationic liposome delivery vehicle.
13. The method of claim 12 , further comprising concurrently or sequentially administering an isolated nucleic acid molecule encoding a glycoprotein D (gD) in an adjuvant.
14. The method of claim 12 , wherein the cationic liposome delivery vehicle comprises one of the following combinations: DOTAP and cholesterol; DOTMA and cholesterol; DDAB and cholesterol; or DOTIM and cholesterol.
15. The composition of any one of claims 1 , 2 , 3 , 4 , or 6 - 9 , further comprising a pharmaceutically acceptable excipient.
16. The composition of claim 15 , wherein the excipient comprises a non-ionic diluent.
17. The composition of claim 15 , wherein the excipient is 5 percent (w/v) dextrose in water.