Methods for preventing dengue and hepatitis a

A method of effective vaccination against hepatitis A and dengue disease in a subject or subject population, the method comprising, simultaneously on the same day administering a hepatitis A vaccine and a unit dose of a tetravalent dengue virus composition to the subject or the subject population, wherein the unit dose comprises four live attenuated dengue virus serotypes

• wherein the unit dose is lyophilized and upon reconstitution with 0.5 mL of a pharmaceutically acceptable diluent comprises:
• (i) a chimeric dengue serotype 2/1 strain, in a concentration of at least 3.3 log 10 pfu/0.5 ml,
• (ii) a dengue serotype 2 strain, in a concentration of at least 2.7 log 10 pfu/0.5 ml,
• (iii) a chimeric dengue serotype 2/3 strain, in a concentration of at least 4.0 log 10 pfu/0.5 ml, and
• (iv) a chimeric dengue serotype 2/4 strain, in a concentration of at least 4.5 log 10 pfu/0.5 ml,
• wherein the four live attenuated dengue virus serotypes are defined by at least one of the following:
• (1) a 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 2/3 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 2/3 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 2/3 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 2/3 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.