A fragment of the envelope protein from dengue-1 virus, fused in two different sites of the meningococcal P64k protein carrier, induces a functional immune response in mice.
Previously we have reported the capacity of the fusion protein PD3, composed of the P64k protein and the envelope (E) fragment from amino acids (aa) 286-426 of dengue-2 virus (DEN-2), to induce a functional immune response in mice against the homologous virus. In that case, the E fragment was inserted within the lipoyl-binding domain of the meningococcal P64k protein. In the present study, to test the functionality of the same E region from dengue-1 (DEN-1), a similar construct was made. Furthermore, another alternative of fusion protein was also constructed where the same E fragment from DEN-1 was fused to the C-terminus of the P64k protein. The recombinant proteins obtained (PD11 and PD10) were semi-purified and analysed for their antigenicity, immunogenicity and the ability to protect mice against lethal challenge. Both molecules exhibited the same recognition patterns against anti-DEN-1 polyclonal antibodies. In addition, when administered to mice, they elicited high levels of neutralizing antibodies and induced significant protection against lethal challenge with DEN-1 after intracerebral inoculation. These results reveal the availability of two sites within the P64k for the further insertion of DEN fragments, enabling a construct carrying two fragments from heterologous serotypes within the same molecule of this protein carrier.
Hermida
Lisset
L
Centro de Ingeniería Genética y Biotecnología, Habana, Cuba. lisset.hermida@cigb.edu.cu
Rodríguez
Rayner
R
Lazo
Laura
L
Bernardo
Lídice
L
Silva
Ricardo
R
Zulueta
Aída
A
López
Carlos
C
Martín
Jorge
J
Valdés
Iris
I
del Rosario
Delfina
D
Guillén
Gerardo
G
Guzmán
María G
MG
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D003715:Dengue / Q000517:prevention & control; D003716:Dengue Virus / Q000737:chemistry*; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage
D001425:Bacterial Outer Membrane Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C112623:lpdA protein, Neisseria meningitidis