Methods and compositions for treating herpes
The present disclosure provides certain combinations of immunogenic compositions against HSV-2 and antiviral therapy. The vaccines can be used therapeutically and/or prophylactically.
1. A method of treating HSV-1 and/or HSV-2 infection in a subject, the method comprising:
administering an antiviral therapy to a subject receiving a vaccine formulation, so that efficacy of the vaccine formulation and/or the antiviral therapy is improved in the subject over a specified time period relative to a subject receiving only the vaccine formulation or the antiviral therapy;
wherein the vaccine formulation comprises an HSV-2 gD2 polypeptide, wherein the gD2 polypeptide has an internal deletion of all or part of the transmembrane domain, and an HSV-2 ICP4 polypeptide or an immunogenic fragment comprising at least 8 contiguous amino acids of HSV-2 ICP4 polypeptide;
wherein the antiviral therapy comprises famciclovir, valaciclovir, aciclovir or a combination thereof;
wherein the antiviral therapy is administered during and/or prior to the subject receiving the vaccine formulation; and
wherein the efficacy of the vaccine formulation and/or the antiviral therapy is measured or indicated by a decrease of one or more herpes signs or symptoms or increased health-related quality of life.
2. The method of claim 1 , further comprising administering the antiviral therapy to one or more additional subjects receiving the vaccine formulation, wherein the antiviral therapy is administered during and/or prior to the subject receiving the vaccine formulation.
3. The method of claim 2 , wherein the efficacy of the vaccine formulation and/or the antiviral therapy is improved in the one or more additional subjects over a specified time period relative to subjects receiving only the vaccine formulation or the antiviral therapy.
4. The method of claim 3 , wherein the efficacy of the vaccine formulation and/or the antiviral therapy is measured or indicated by an increase in a proportion of subjects who exhibit a decrease in one or more herpes signs or symptoms, and/or an increase in health-related quality of life.
5. A method of treating HSV-1 and/or HSV-2 infection in a subject, the method comprising:
administering a vaccine formulation to a subject receiving or who has received an antiviral therapy, so that efficacy of the vaccine formulation and/or antiviral therapy is improved in the subject over a specified time period relative to a subject receiving only the vaccine formulation or the antiviral therapy;
wherein the vaccine formulation comprises an HSV-2 gD2 polypeptide, wherein the gD2 polypeptide has an internal deletion of all or part of the transmembrane domain and an HSV-2 ICP4 polypeptide or an immunogenic fragment comprising at least 8 contiguous amino acids of HSV-2 ICP4 polypeptide;
wherein the antiviral therapy comprises famciclovir, valaciclovir, aciclovir or a combination thereof;
wherein the vaccine formulation is administered during the subject receiving and/or after the subject has received the antiviral therapy; and
wherein the efficacy of the vaccine formulation and/or the antiviral therapy is measured or indicated by a decrease of one or more herpes signs or symptoms or increased health-related quality of life.
6. The method of claim 5 , further comprising administering the vaccine formulation to one or more additional subjects receiving or who have received the antiviral therapy.
7. The method of claim 6 , wherein the efficacy of the vaccine formulation and/or the antiviral therapy is improved in the one or more additional subjects over a specified time period relative to subjects receiving only the vaccine formulation or the antiviral therapy.
8. The method of claim 7 , wherein the efficacy of the vaccine formulation and/or the antiviral therapy is measured or indicated by an increase in one or more herpes signs or symptoms and/or an increase in health-related quality of life.
9. A method of treating HSV-1 and/or HSV 2 infection in a subject, the method comprising:
administering a vaccine formulation to a subject receiving or who has received antiviral therapy, so that efficacy of the antiviral therapy is improved in the subject over a specified time period relative to a subject receiving only the antiviral therapy;
wherein the vaccine formulation comprises an HSV-2 gD2 polypeptide, wherein the gD2 polypeptide has an internal deletion of all or part of the transmembrane domain and an HSV-2 ICP4 polypeptide or an immunogenic fragment comprising at least 8 contiguous amino acids of HSV-2 ICP4 polypeptide;
wherein the antiviral therapy comprises famciclovir, valaciclovir, aciclovir or a combination thereof;
wherein the vaccine formulation is administered during the subject receiving and/or after the subject has received the antiviral therapy; and
wherein the efficacy of the antiviral therapy is measured or indicated by decreased lesion score.
10. The method of claim 9 , further comprising administering the vaccine formulation to one or more additional subjects receiving or who have received the antiviral therapy.
11. The method of claim 10 , wherein the efficacy of the antiviral therapy is improved in the one or more additional subjects over a specified time period relative to subjects receiving only the antiviral therapy.
12. The method of claim 11 , wherein the efficacy of the antiviral therapy is measured or indicated by an increased proportion of subjects who exhibit decreased lesion score.
13. The method of claim 1 , wherein the efficacy of the vaccine formulation and/or antiviral therapy is assessed at, at least 3 months, 6 months, 12 months, 18 months, 24 months, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years after administration of therapy.
14. The method of claim 1 , wherein the decrease in one or more herpes signs or symptoms is a decrease in the percentage of days with herpes-related signs or symptoms and/or a decrease in the magnitude of herpes-related signs or symptoms.
15. The method of claim 1 , wherein the efficacy of the vaccine formulation is measured or indicated by an increase in humoral response and/or an increase in cellular response.
16. The method of claim 1 , wherein the subject: is not receiving therapy comprising tenofovir, lysine, a supplement or medication, other than valacyclovir; does not have a history of ocular herpes infection, herpes-related erythema multiforme, herpes meningitis or herpes encephalitis; does not have active genital HSV-2 lesions; is not immunocompromised; is not receiving systemic immunosuppressive medication; does not have an autoimmune disease; has not previously had an autoimmune disease; does not have HIV, hepatitis B or hepatitis C; does not have history of hypersensitivity to any component of the vaccine formulation; does not have a clinically significant laboratory abnormality except for (i) creatinine kinase in subjects with an identified exercise regimen and hepatic and renal enzyme levels within normal limits or (ii) isolated Grade 2 unconjugated bilirubin in fasting subjects with a history of Gilbert's syndrome; has not received any other vaccine containing an HSV-2 antigen; has not received an investigational product within 30 days prior to the first dose of the vaccine formulation; has not received a blood product within 90 days prior to the first dose of the vaccine formulation; has not received a live vaccine within 28 days prior to the first dose of the vaccine formulation; has not received any other vaccine within 14 days prior to the first dose of the vaccine formulation; does not receive any other vaccine from the first dose until 28 days after the third dose; is not pregnant or nursing; or any combination thereof.
17. The method of claim 1 , wherein the subject: is male, female or non-pregnant female; is at least 18 years old and less than 51 years old, is at least 10, 11, 12, 13, 14, 15, 16 or 17 years old, or is 51 years or older; is receiving antiviral therapy; has a history of at least one genital herpes outbreak while on antiviral therapy within 6 months of treatment; has a history of greater than 5 outbreaks of genital herpes within one year if not receiving antiviral therapy; has been diagnosed with genital herpes infection for greater than 1 year; uses contraception for 28 days before and 90days after treatment with the vaccine formulation; or any combination thereof.
18. The method of claim 1 , further comprising administering the vaccine formulation concurrently with or following administration of the antiviral therapy.
19. The method of claim 1 , wherein the vaccine formulation comprises an HSV-2 gD2 polypeptide comprising an amino acid sequence having at least 85%, 90%, 95%, 97%, 98%, or 99% identity to SEQ ID NO:4, and an HSV-2 ICP4 polypeptide comprising an amino acid sequence having at least 85%, 90%, 95%, 97%, 98%, or 99% identity to SEQ ID NO:2.
20. The method of claim 1 , wherein the vaccine formulation comprises an adjuvant.
21. The vaccine formulation of claim 20 , wherein the adjuvant comprises one or more saponin fractions.
22. The method of claim 1 , wherein the subject receives suppressive antiviral therapy.
23. The method of claim 18 , wherein the vaccine formulation is administered in at least one dose, at least two doses, at least three doses, at least four doses, at least 5 doses or more.
24. The method of claim 18 , wherein the vaccine formulation is administered at intervals of about 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, 56 days or longer.
25. The method of claim 1 , wherein the HSV-1 and/or HSV-2 infection is a genital herpes infection.
26. The method of claim 1 , wherein the vaccine formulation comprises about 10 μg, 20 μg, 30 μg, 60 μg, or 100 μg of each of the gD2 polypeptide and the ICP4 polypeptide and/or about 25 μg, 50 μg or 75 μg of adjuvant.
27. The method of claim 26 , wherein the vaccine formulation comprises about 60 μg of the gD2 polypeptide, about 60 μg of the ICP4 polypeptide and about 50 μg of adjuvant.