Compositions for booster vaccination against dengue

A method of inducing in a human subject a neutralizing antibody response against dengue virus, said method comprising administering to said human subject a composition comprising a dengue antigen of each of serotypes 1 to 4, wherein said dengue antigens of serotypes 1 to 4 are each independently selected from the group consisting of a live attenuated dengue virus and a live attenuated chimeric dengue virus, wherein said dengue antigens of serotypes 1 to 4 comprise nucleic acid sequences having at least 90% identity to SEQ ID NOs:

• 1, 2, 3 and 4 respectively;
• wherein
• the amino acid at position 226 of the Envelope (E) protein of the dengue antigen of serotype 2 is threonine,
• the amino acid at position 228 of the Envelope (E) protein of the dengue antigen of serotype 2 is glycine, and
• the amino acid at position 251 of the Envelope (E) protein of the dengue antigen of serotype 2 is valine,
• wherein said composition is administered as:
• (a) a primary vaccination, followed at least 1 year after the end of the primary vaccination course by
• (b) a booster vaccination,
• and wherein the human subject is initially dengue naïve.

A method of booster vaccination for inducing in a human subject a neutralizing antibody response against dengue virus, said method comprising administering to said human subject a composition comprising a dengue antigen of each of serotypes 1 to 4 wherein each of said dengue antigens is independently selected from the list consisting of:

• (a) a live attenuated dengue virus and (b) a live attenuated chimeric dengue virus,
• wherein said subject has previously received a primary vaccination course against each of serotypes 1 to 4 of dengue virus, and said subject was dengue naïve before said primary vaccination course,
• wherein said booster vaccination is administered at least one year after the end of the primary vaccination course and results in at least a 2-fold increase in the neutralizing antibody titre against each of serotypes 1 to 4;
• wherein said dengue antigens of serotypes 1, 3 and 4 comprise nucleic acid sequences having at least 90% identity to SEQ ID NOs:
• 1, 3 and 4 respectively, wherein said dengue antigen of serotype 2 comprises a nucleic acid sequence having at least 95% identity to SEQ ID No:
• 2;
• and
• wherein Envelope (E) protein encoded by the nucleic acid sequence of the dengue antigen of serotype 2 comprises a threonine residue at the position within the protein which correspondence to position 226 of SEQ ID NO:
• 2, a glycine residue at the position within the protein which corresponds to position 228 of SEQ ID NO:
• 2 and a valine residue at the position within the protein which corresponds to position 251 of SEQ ID NO:
• 2.

A method of inducing in a human subject a neutralizing antibody response against dengue virus, said method comprising administering to said human subject a composition comprising a dengue antigen of each of serotypes 1 to 4, wherein said dengue antigens of serotypes 1 to 4 are each independently selected from the group consisting of a live attenuated dengue virus and a live attenuated chimeric dengue virus, wherein said dengue antigens of serotypes 1, 3 and 4 comprise nucleic acid sequences having at least 90% identity to SEQ ID NOs:

• 1, 3 and 4 respectively,
• wherein said dengue antigen of serotype 2 comprises a nucleic acid sequence having at least 95% identity to SEQ ID No:
• 2;
• and
• wherein Envelope (E) protein encoded by the nucleic acid sequence of the dengue antigen of serotype 2 comprises a threonine residue at the position within the protein which correspondence to position 226 of SEQ ID NO:
• 2, a glycine residue at the position within the protein which corresponds to position 228 of SEQ ID NO:
• 2 and a valine residue at the position within the protein which corresponds to position 251 of SEQ ID NO:
• 2,
• wherein said composition is administered as:
• (a) a primary vaccination, followed at least 1 year after the end of the primary vaccination course by
• (b) a booster vaccination,
• and wherein the human subject is initially dengue naïve.