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.
Claims17
A method of vaccinating against virologically confirmable dengue disease in a subject population, 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 18 months after a second unit dose administration of a tetravalent dengue virus composition wherein the method comprises a primary vaccination comprising:
- selecting a subject from the subject population without determining whether the subject had a previous dengue infection,
- administering a first unit dose of the tetravalent dengue virus composition to the subject population comprising seropositive subjects, seronegative subjects, or a combination thereof, the tetravalent dengue virus composition comprising four dengue virus strains representing serotype 1, serotype 2, serotype 3 and serotype 4, and
- administering a second unit dose of the tetravalent dengue virus composition to the subject population within 3 months of administration of the first unit dose,
- wherein the first dose and the second dose each comprises 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
- b) NS1-53 Gly-to-Asp
- c) NS3-250 Glu-to-Val;
- 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,
- and wherein the first unit dose corresponding to a dose of 0.5 ml comprising:
- (i) the dengue serotype 1 has a concentration of at least 3.3 log 10 pfu/0.5 mL,
- (ii) the dengue serotype 2 has a concentration of at least 2.7 log 10 pfu/0.5 mL,
- (iii) the dengue serotype 3 has a concentration of at least 4.0 log 10 pfu/0.5 mL, and
- (iv) the dengue serotype 4 has a concentration of at least 4.5 log 10 pfu/0.5 mL, and the second unit dose corresponding to a dose of 0.5 ml comprising:
- (i) the dengue serotype 1 has a concentration of at least 3.3 log 10 pfu/0.5 mL,
- (ii) the dengue serotype 2 has a concentration of at least 2.7 log 10 pfu/0.5 mL,
- (iii) the dengue serotype 3 has a concentration of at least 4.0 log 10 pfu/0.5 mL, and
- (iv) the dengue serotype 4 has a concentration of at least 4.5 log 10 pfu/0.5 mL.
A method of vaccinating against virologically confirmable dengue disease with hospitalization in subjects, the method providing a combined vaccine efficacy against virologically confirmable dengue disease with hospitalization of at least 65% which is represented by a reduction of at least 65% dengue disease with hospitalization occurrence in vaccinated subjects compared to unvaccinated subjects, in each of seropositive subjects and seronegative subjects, for at least 18 months after a second unit dose administration, by administering a tetravalent dengue virus composition including four live attenuated dengue virus strains representing serotype 1, serotype 2, serotype 3 and serotype 4, the method comprises a primary vaccination consisting of the steps of:
- administering a first unit dose of the tetravalent dengue virus composition to the subject population comprising seropositive subjects, seronegative subjects, or a combination thereof, and
- administering a second unit dose of the tetravalent dengue virus composition to the subject population within 3 months of administration of the first unit dose,
- wherein the first dose and the second dose each comprises 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)
- b) NS1-53 Gly-to-Asp
- c) NS3-250 Glu-to-Val;
- 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,
- and wherein the first unit dose corresponding to a dose of 0.5 ml comprising:
- (i) the dengue serotype 1 has a concentration of at least 3.3 log 10 pfu/0.5 mL,
- (ii) the dengue serotype 2 has a concentration of at least 2.7 log 10 pfu/0.5 mL,
- (iii) the dengue serotype 3 has a concentration of at least 4.0 log 10 pfu/0.5 mL, and
- (iv) the dengue serotype 4 has a concentration of at least 4.5 log 10 pfu/0.5 mL, and
- the second unit dose corresponding to a dose of 0.5 ml comprises:
- (i) the dengue serotype 1 has a concentration of at least 3.3 log 10 pfu/0.5 mL,
- (ii) the dengue serotype 2 has a concentration of at least 2.7 log 10 pfu/0.5 mL,
- (iii) the dengue serotype 3 has a concentration of at least 4.0 log 10 pfu/0.5 mL, and
- (iv) the dengue serotype 4 has a concentration of at least 4.5 log 10 pfu/0.5 mL.
Dependencies are inferred from the claim text.