Dengue-4 envelope domain III fused twice within the meningococcal P64k protein carrier induces partial protection in mice.
A vaccine against dengue virus must be able to induce an effective and equivalent immune response to the four viral serotypes; however, some studies have revealed that DEN4 (dengue-virus serotype 4) induces a weaker immune response than the others in quadrivalent (tetravalent') formulations. We have previously reported the protective capacity, in a viral encephalitis murine model, of fusion protein P64k-envelope domain III of DEN1, DEN2 and DEN3. We also reported that the P64k protein can be used as a carrier in two different positions: the insertion following the first 45 amino acids and the fusion at the C-terminus. Considering the low immunogenicity described for DEN4, in the present study we obtained a novel chimaeric protein by inserting two dengue-4 envelope domains III in both sites of P64k (PD24), and hence increasing the presence of the virus in the final construct. After expression in Escherichia coli and semipurification, the protein exhibited a pattern of high molecular mass and was well recognized by human and murine polyclonal antibodies. The protein was finally evaluated in mice, Al(OH)(3) being employed as the adjuvant. Even though the animals exhibited low levels of antiviral antibodies, the recombinant protein induced significant protection against lethal challenge with dengue-4 virus.
Lazo
Laura
L
Center for Genetic Engineering and Biotechnology. PO Box 6162, Havana 10 600, Cuba. laura.lazo@cigb.edu.cu
Zulueta
Aída
A
Hermida
Lisset
L
Blanco
Aracelys
A
Sánchez
Jorge
J
Valdés
Iris
I
Gil
Lázaro
L
López
Carlos
C
Romero
Yaremis
Y
Guzmán
María G
MG
Guillén
Gerardo
G
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D003715:Dengue / Q000517:prevention & control* / Q000821:virology*; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D053059:Dengue Vaccines; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C466981:glycoprotein E, dengue virus type 4; C112623:lpdA protein, Neisseria meningitidis