Dengue vaccine unit dose and administration thereof

A method for vaccinating against dengue disease in a subject or a population of subjects, the method comprising, administering one unit dose of a dengue virus composition, wherein the administration of the one unit dose to the subject or the subject population results in 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, wherein the dengue virus composition is lyophilized and upon reconstitution with 0.5 mL of at least one pharmaceutically acceptable diluent comprises:

• (i) a chimeric dengue serotype 2/1 strain, in a concentration of at least 3.3 log10 pfu/0.5 ml,
• (ii) a dengue serotype 2 strain, in a concentration of at least 2.7 log10 pfu/0.5 ml,
• (iii) a chimeric dengue serotype ⅔ strain, in a concentration of at least 4.0 log10 pfu/0.5 ml, and
• (iv) a chimeric dengue serotype 2/4 strain, in a concentration of at least 4.5 log10 pfu/0.5 ml, wherein upon reconstitution with a pharmaceutically acceptable diluent, (i), (ii), (iii), and (iv) provide a total concentration of pfu/0.5 ml and based on said total concentration of pfu/0.5 ml, the concentration of (i) in pfu/0.5 ml is at least 1%, the concentration of (ii) in pfu/0.5 ml is less than 10%, the concentration of (iii) in pfu/0.5 ml is at least 10%, and the concentration of (iv) in pfu/0.5 ml is at least 50%.

A method for vaccinating against dengue disease in a subject or a population of subjects, the method comprising, administering one unit dose of a dengue virus composition, wherein the administration of the one unit dose to the subject or the subject population results in 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, wherein the dengue virus composition comprises:

• four live attenuated dengue virus serotypes, wherein the dengue virus composition is lyophilized and upon reconstitution with 0.5 mL of at least one pharmaceutically acceptable diluent comprises:
• (i) a chimeric dengue serotype 2/1 strain, in a concentration of at least 3.3 log10 pfu/0.5 ml,
• (ii) a dengue serotype 2 strain, in a concentration of at least 2.7 log10 pfu/0.5 ml,
• (iii) a chimeric dengue serotype ⅔ strain, in a concentration of at least 4.0 log10 pfu/0.5 ml, and
• (iv) a chimeric dengue serotype 2/4 strain, in a concentration of at least 4.5 log10 pfu/0.5 ml, wherein upon reconstitution with at least one pharmaceutically acceptable diluent, (i), (ii), (iii), and (iv) provide a total concentration of pfu/0.5 ml and based on said total concentration of pfu/0.5 ml, the concentration of (i) in pfu/0.5 ml is at least 1%, the concentration of (ii) in pfu/0.5 ml is less than 10%, the concentration of (iii) in pfu/0.5 ml is at least 10%, and the concentration of (iv) in pfu/0.5 ml is at least 50%,
• wherein the four live attenuated dengue virus serotypes are defined by the following:
• (1) the dengue serotype 2 strain which is derived from the wild type virus strain DEN-2 16681 and differs in at least three nucleotides from the wild type as follows:
• a) 5′-noncoding region (NCR)-57,
• b) NS1-53 Gly-to-Asp, and
• c) NS3-250 Glu-to-Val;
• and
• wherein the three chimeric dengue strains are derived from the dengue serotype 2 strain by replacing the structural proteins prM and E from the dengue serotype 2 strain with the corresponding structural proteins from the other dengue serotypes, resulting in the following chimeric dengue strains:
• the chimeric dengue serotype 2/1 strain,
• the chimeric dengue serotype ⅔ strain, and
• the chimeric dengue serotype 2/4 strain;
• (2) the chimeric dengue serotype 2/1 strain comprising a nucleotide sequence according to SEQ ID NO:
• 1,
• the dengue serotype 2 strain comprising a nucleotide sequence according to SEQ ID NO:
• 3,
• the chimeric dengue serotype ⅔ strain comprising a nucleotide sequence according to SEQ ID NO:
• 5, and
• the chimeric dengue serotype 2/4 strain comprising a nucleotide sequence according to SEQ ID NO:
• 7;
• (3) the chimeric dengue serotype 2/1 strain comprising the structural proteins provided in the amino acid sequence of SEQ ID NO:
• 2,
• the dengue serotype 2 strain comprising the structural proteins provided in the amino acid sequence of SEQ ID NO:
• 4,
• the chimeric dengue serotype ⅔ strain comprising the structural proteins provided in the amino acid sequence of SEQ ID NO:
• 6, and
• the chimeric dengue serotype 2/4 strain comprising the structural proteins provided in the amino acid sequence of SEQ ID NO:
• 8, and
• (4) the chimeric dengue serotype 2/1 strain comprising a nucleotide sequence encoding the amino acid sequence SEQ ID NO:
• 2,
• the dengue serotype 2 strain comprising a nucleotide sequence encoding the amino acid sequence SEQ ID NO:
• 4,
• the chimeric dengue serotype ⅔ strain comprising a nucleotide sequence encoding the amino acid sequence SEQ ID NO:
• 6, and
• the chimeric dengue serotype 2/4 strain comprising a nucleotide sequence encoding the amino acid sequence SEQ ID NO:
• 8.