Dengue vaccine unit dose and administration thereof
AssigneeTakeda Vaccines, Inc.
InventorDerek Wallace
Life of this patent
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Abstract
The invention relates to a unit dose of a dengue vaccine composition and methods and uses for preventing dengue disease and methods for stimulating an immune response to all four dengue virus serotypes in a subject or subject population. The unit dose of a dengue vaccine composition includes constructs of each dengue serotype, such as TDV-1, TDV-2, TDV-3 and TDV-4, at various concentrations in order to improve protection from dengue infection.
Claims19
A method of vaccinating against virologically confirmable dengue disease in subjects aged 4 to 60 years of age, the method providing a combined vaccine efficacy of at least 60% which is represented by at least 60% reduction in dengue disease occurrence in vaccinated subjects compared to unvaccinated subjects, in each of seropositive subjects and seronegative subjects, for at least 12 months after a second unit dose administration, by administering to a subject population of seropositive subjects, seronegative subjects, or a combination thereof, a tetravalent dengue virus composition including four dengue virus strains representing serotype 1, serotype 2, serotype 3 and serotype 4, represented by a chimeric dengue serotype 2/1 strain, a dengue serotype 2 strain, a chimeric dengue serotype 2/3 strain, and a chimeric dengue serotype 2/4 strain, the dengue serotype 2 strain being derived from the wild type virus strain DEN-2 16681 and differing in at least three nucleotides from the wild type as follows:
- a) 5′-noncoding region (NCR)-57 (nt-57 C-to-T)
- b) NS1-53 Gly-to-Asp (nt-2579 G-to-A)
- c) NS3-250 Glu-to-Val (nt-5270 A-to-T);
- and
- the three chimeric dengue strains being derived from the serotype 2 strain by replacing the structural proteins prM and E from serotype 2 strain with the corresponding structural proteins from the other dengue serotypes, resulting in the following chimeric dengue strains:
- a DENV-2/1 chimera,
- a DENV-2/3 chimera and
- a DENV-2/4 chimera,
- the method consisting of:
- selecting a subject without determining whether the subject had a previous dengue infection,
- subcutaneously administering a first unit dose of said tetravalent dengue vaccine composition to said subject, the first unit dose corresponding to a dose of 0.5 ml comprising
- (i) the dengue serotype 1 with a concentration of at least 3.3 log 10 pfu/0.5 mL,
- (ii) the dengue serotype 2 with a concentration of at least 2.7 log 10 pfu/0.5 mL,
- (iii) the dengue serotype 3 with a concentration of at least 4.0 log 10 pfu/0.5 mL, and
- (iv) the dengue serotype 4 with a concentration of at least 4.5 log 10 pfu/0.5 mL,
- subcutaneously administering to said subject a second unit dose of said tetravalent dengue vaccine composition within 3 months after the first unit dose, the second unit dose corresponding to a dose of 0.5 ml comprising
- (i) the dengue serotype 1 with a concentration of at least 3.3 log 10 pfu/0.5 mL,
- (ii) the dengue serotype 2 with a concentration of at least 2.7 log 10 pfu/0.5 mL,
- (iii) the dengue serotype 3 with a concentration of at least 4.0 log 10 pfu/0.5 mL, and
- (iv) the dengue serotype 4 with a concentration of at least 4.5 log 10 pfu/0.5 mL,
- and optionally administering a booster dose of said tetravalent dengue vaccine composition to said subject at least 12 months after administration of the second unit dose.
A method of vaccinating against virologically confirmable dengue disease with hospitalization in subjects aged 4 to 60 years of age, the method providing a combined vaccine efficacy against virologically confirmable dengue disease with hospitalization of at least 70% which is represented by a reduction of at least 70% dengue disease with hospitalization occurrence in vaccinated subjects aged 4 to 60 years compared to unvaccinated subjects, in each of seropositive subjects and seronegative subjects, for at least 12 months after a second unit dose administration, by administering to a subject population of seropositive subjects, seronegative subjects, or a combination thereof a tetravalent dengue virus composition including four dengue virus strains representing serotype 1, serotype 2, serotype 3 and serotype 4, represented by a chimeric dengue serotype 2/1 strain, a dengue serotype 2 strain, a chimeric dengue serotype 2/3 strain, and a chimeric dengue serotype 2/4 strain,
- the dengue serotype 2 strain being derived from the wild type virus strain DEN-2 16681 and differing in at least three nucleotides from the wild type as follows:
- a) 5′-noncoding region (NCR)-57 (nt-57 C-to-T)
- b) NS1-53 Gly-to-Asp (nt-2579 G-to-A)
- c) NS3-250 Glu-to-Val (nt-5270 A-to-T);
- and
- the three chimeric dengue strains being derived from the serotype 2 strain by replacing the structural proteins prM and E from serotype 2 strain with the corresponding structural proteins from the other dengue serotypes, resulting in the following chimeric dengue strains:
- a DENV-2/1 chimera,
- a DENV-2/3 chimera and
- a DENV-2/4 chimera,
- the method consisting of:
- selecting a subject without determining whether the subject had a previous dengue infection,
- subcutaneously administering a first unit dose of said tetravalent dengue vaccine composition to said subject, the first unit dose corresponding to a dose of 0.5 ml comprising
- (i) the dengue serotype 1 with a concentration of at least 3.3 log 10 pfu/0.5 mL,
- (ii) the dengue serotype 2 with a concentration of at least 2.7 log 10 pfu/0.5 mL,
- (iii) the dengue serotype 3 with a concentration of at least 4.0 log 10 pfu/0.5 mL, and
- (iv) the dengue serotype 4 with a concentration of at least 4.5 log 10 pfu/0.5 mL,
- subcutaneously administering to said subject a second unit dose of said tetravalent dengue vaccine composition within 3 months after the first unit dose, the second unit dose corresponding to a dose of 0.5 ml comprising
- (i) the dengue serotype 1 with a concentration of at least 3.3 log 10 pfu/0.5 mL,
- (ii) the dengue serotype 2 with a concentration of at least 2.7 log 10 pfu/0.5 mL,
- (iii) the dengue serotype 3 with a concentration of at least 4.0 log 10 pfu/0.5 mL, and
- (iv) the dengue serotype 4 with a concentration of at least 4.5 log 10 pfu/0.5 mL,
- and optionally administering a booster dose of said tetravalent dengue vaccine composition to said subject at least 12 months after administration of the second unit dose.
Dependencies are inferred from the claim text.