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Vaccines in development against West Nile virus.

Brandler S, Tangy F - Viruses (2013)

Bottom Line: In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine.MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines.A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génomique Virale et Vaccination, INSTITUT PASTEUR, 28 rue du Dr Roux, Paris 75015, France. samantha.brandler@pasteur.fr.

ABSTRACT
West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

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Related in: MedlinePlus

Schwarz/Moraten vaccine strain (MVSchw)-sEWNV vector. The MV genes are indicated: N (nucleoprotein), PVC (phosphoprotein and V/C proteins), M (matrix), F (fusion), H (hemagglutinin), L (polymerase). T7 = T7 RNA polymerase promoter; hh = hammerhead ribozyme; T7t = T7 RNA polymerase terminator; ∂ = hepatitis delta virus (HDV) ribozyme; in red, the additional transcription units (ATU1) with the WNV sequence inserted. Total nucleotides in measles virus (MV) genome: 15,894.
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viruses-05-02384-f001: Schwarz/Moraten vaccine strain (MVSchw)-sEWNV vector. The MV genes are indicated: N (nucleoprotein), PVC (phosphoprotein and V/C proteins), M (matrix), F (fusion), H (hemagglutinin), L (polymerase). T7 = T7 RNA polymerase promoter; hh = hammerhead ribozyme; T7t = T7 RNA polymerase terminator; ∂ = hepatitis delta virus (HDV) ribozyme; in red, the additional transcription units (ATU1) with the WNV sequence inserted. Total nucleotides in measles virus (MV) genome: 15,894.

Mentions: The infectious cDNA of the widely used Schwarz/Moraten vaccine strain (MVSchw) allows the production of the Schwarz/Moraten vaccine without having to depend on the availability of seed stocks [97]. Additional transcription units (ATU) were introduced in the viral genome to turn it into a vector expressing foreign proteins (Figure 1). The expression of additional open-reading frames (ORFs) inserted in an ATU is controlled by cis-acting elements modeled after those present in the nucleocapsid /phosphoprotein boundary region (allowing for the necessary transient transcription stop upstream of the transgene, autonomous transcription, capping and polyadenylation of the transgene). Three vectors allow insertion of foreign genes in three different positions of the MV genome: one upstream the N gene, one between the P and M genes, and one between the H and L genes. Single vectors can be produced that express single antigens, and recombination of these vectors generates multiple vectors that express two or three different foreign genes.


Vaccines in development against West Nile virus.

Brandler S, Tangy F - Viruses (2013)

Schwarz/Moraten vaccine strain (MVSchw)-sEWNV vector. The MV genes are indicated: N (nucleoprotein), PVC (phosphoprotein and V/C proteins), M (matrix), F (fusion), H (hemagglutinin), L (polymerase). T7 = T7 RNA polymerase promoter; hh = hammerhead ribozyme; T7t = T7 RNA polymerase terminator; ∂ = hepatitis delta virus (HDV) ribozyme; in red, the additional transcription units (ATU1) with the WNV sequence inserted. Total nucleotides in measles virus (MV) genome: 15,894.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814594&req=5

viruses-05-02384-f001: Schwarz/Moraten vaccine strain (MVSchw)-sEWNV vector. The MV genes are indicated: N (nucleoprotein), PVC (phosphoprotein and V/C proteins), M (matrix), F (fusion), H (hemagglutinin), L (polymerase). T7 = T7 RNA polymerase promoter; hh = hammerhead ribozyme; T7t = T7 RNA polymerase terminator; ∂ = hepatitis delta virus (HDV) ribozyme; in red, the additional transcription units (ATU1) with the WNV sequence inserted. Total nucleotides in measles virus (MV) genome: 15,894.
Mentions: The infectious cDNA of the widely used Schwarz/Moraten vaccine strain (MVSchw) allows the production of the Schwarz/Moraten vaccine without having to depend on the availability of seed stocks [97]. Additional transcription units (ATU) were introduced in the viral genome to turn it into a vector expressing foreign proteins (Figure 1). The expression of additional open-reading frames (ORFs) inserted in an ATU is controlled by cis-acting elements modeled after those present in the nucleocapsid /phosphoprotein boundary region (allowing for the necessary transient transcription stop upstream of the transgene, autonomous transcription, capping and polyadenylation of the transgene). Three vectors allow insertion of foreign genes in three different positions of the MV genome: one upstream the N gene, one between the P and M genes, and one between the H and L genes. Single vectors can be produced that express single antigens, and recombination of these vectors generates multiple vectors that express two or three different foreign genes.

Bottom Line: In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine.MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines.A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génomique Virale et Vaccination, INSTITUT PASTEUR, 28 rue du Dr Roux, Paris 75015, France. samantha.brandler@pasteur.fr.

ABSTRACT
West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

Show MeSH
Related in: MedlinePlus