Amino acid changes in the recombinant Dengue 3 Envelope domain III determine its antigenicity and immunogenicity in mice.
The immunogenicity of the Envelope fragment from amino acid 284 to 426 of Dengue viruses, obtained as fusion proteins with P64k in Escherichia coli, has been previously tested by our group. Here, we studied two fusion proteins with P64k carrying the Envelope fragment from two strains of Dengue 3: H87 prototype strain (PD9) and an isolate from the Nicaragua 1994 outbreak (PD18). Sequence comparison of the Dengue Envelope fragments showed four amino acid differences. Only PD18 reacted with human antisera and induced a higher functional immune response in mice than PD9. Moreover, mice immunized with PD18 were less susceptible to Dengue 3 administered intracerebrally than those immunized with PD9. The results reveal that not all sequences of the Dengue Envelope fragment, at least in the context of P64k, are antigenic and generate a functional immune response against the native virus. This finding has direct implications for the design of vaccines based on fragments of the Envelope protein.
Zulueta
Aída
A
Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31 E/158 y 190, P.O. Box 6162, CP 10600, Cubanacán, Playa, Havana, Cuba. aida.zulueta@cigb.edu.cu
Martín
Jorge
J
Hermida
Lisset
L
Alvarez
Mayling
M
Valdés
Iris
I
Prado
Irina
I
Chinea
Glay
G
Rosario
Delfina
D
Guillén
Gerardo
G
Guzmán
María G
MG
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D007114:Immunization; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary / Q000235:genetics; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D001425:Bacterial Outer Membrane Proteins; C084188:E protein, Dengue virus type 3; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; C112623:lpdA protein, Neisseria meningitidis