Dengue vaccine unit dose and administration thereof

A method of inoculating a subject against virologically confirmable dengue disease by administering to the subject 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
• 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 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 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 to said subject at least 12 months after administration of the second unit dose.