The present invention is directed to a method of booster vaccination and to a vaccine composition for use in such a method, for inducing in a human subject a neutralizing antibody response, wherein said subject has previously received a primary vaccination against each of serotypes 1 to 4 of dengue virus and was dengue nave before said primary vaccination, said composition comprising a dengue antigen of at least one of serotypes 1 to 4 or a nucleic acid construct capable of expressing said antigens in the subject, wherein said booster vaccination results in a 2-fold increase in the neutralizing antibody titre against each of serotypes 1 to 4. The invention is also directed to a method of inducing in a human subject a neutralizing antibody response comprising the administration of a vaccine composition, or to a vaccine composition for use in such a method, said composition comprising a dengue antigen of each of serotypes 1 to 4, or a nucleic acid construct capable of expressing in said subject a dengue antigen of each of serotypes 1 to 4; wherein said composition is administered as a primary vaccination, followed by a booster vaccination, and wherein the human subject is initially dengue nave.

Chimeric flaviviruses engineered to contain a reporter gene and chimeric nucleic acid molecules encoding the chimeric flaviviruses are described. The chimeric flaviviruses further include genomic non-coding regions, non-structural proteins, and at least a portion of a capsid (C) protein from West Nile virus (WNV), and premembrane (prM) and envelope (E) proteins from dengue virus (DENV). Diagnostic assays that utilize chimeric West Nile/dengue viruses are further described.

Chimeric flaviviruses that include non-coding regions, non-structural proteins, a capsid (C) protein and a portion of a premembrane (prM) signal sequence from West Nile virus (WNV), and a portion of a prM signal sequence, a prM protein and an E protein from Zika virus (VIKV) are described. Also described are compositions and methods for eliciting an immune response in a subject, such as an immune response directed against ZIKV. Diagnostic assays that utilize chimeric West Nile/Zika viruses are further described.

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.

Embodiments herein concern compositions, methods, and uses for inducing an immune response to all four dengue virus serotypes in a child or young adult from about 1 year to about 20 years of age. Some embodiments concern compositions that can include dengue virus chimeras that, either alone or in combination with other constructs, can be used in vaccine compositions against all four dengue virus serotypes. Compositions can include constructs of more than one serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) virus and/or dengue-4 (DEN-4) virus, at various concentrations or ratios to improve protection from infection in children and young adults. In certain embodiments, viruses of the formulations are limited to dengue virus serotypes. Other embodiments concern methods of administering immunogenic compositions against dengue virus that can include chimeric dengue constructs and live, attenuated dengue viruses using single, dual or other regimens.

Compositions for protecting subjects from diseases caused by (+) SS RNA virus are described herein. The compositions include (i) a vector containing a DNA encoding a RNA molecule of an infectious (+) SS RNA virus operably linked to a eukaryotic RNA polymerase promoter and a carrier; or (ii) (+) SS RNA viruses obtained from eukaryotic cells transfected with the vector of (i) and a carrier.

Chimeric flaviviruses that include non-coding regions, non-structural proteins, a capsid (C) protein and a portion of a premembrane (prM) signal sequence from West Nile virus (WNV), and a portion of a prM signal sequence, a prM protein and an E protein from Zika virus (VIKV) are described. Also described are compositions and methods for eliciting an immune response in a subject, such as an immune response directed against ZIKV. Diagnostic assays that utilize chimeric West Nile/Zika viruses are further described.

The present disclosure relates to attenuated Zika viruses and vaccines, attenuated chimeric Zika viruses and vaccines, and to multivalent immunogenic compositions comprising Zika vaccines and vaccines to other flaviviruses. The chimeric Zika viruses includes a first nucleotide sequence encoding at least one structural protein from a Zika virus (ZIKV), a second nucleotide sequence encoding at least one nonstructural protein from a first flavivirus, and a third nucleotide sequence of a 3 untranslated region from a second flavivirus. The multivalent immunogenic compositions comprise an attenuated ZIKV vaccine or an attenuated chimeric ZIKV vaccine (or their combination) together with one or more of a first attenuated virus that is immunogenic against dengue serotype 1, a second attenuated virus that is immunogenic against dengue serotype 2, a third attenuated virus that is immunogenic against dengue serotype 3, and a fourth attenuated virus that is immunogenic against dengue serotype 4. The present disclosure further relates to methods of inducing immune responses, as well as preventing or treating ZIKV infections, and in certain embodiments, the combined prevention or treatment of ZIKV and another flavivirus, e.g., dengue virus.

Compositions for protecting subjects from diseases caused by (+)SS RNA virus are described herein. The compositions include (i) a vector containing a DNA encoding a RNA molecule of an infectious (+)SS RNA virus operably linked to a eukaryotic RNA polymerase promoter and a carrier; or (ii) (+)SS RNA viruses obtained from eukaryotic cells transfected with the vector of (i) and a carrier.

The present invention relates to mutant peptides of the E protein of the West Nile virus and other flaviviruses useful for discriminating flaviviral infections, as well as kits, methods and uses related thereto.