A recombinant fusion protein containing the domain III of the dengue-2 envelope protein is immunogenic and protective in nonhuman primates.
We have previously reported the construction and evaluation in mice of recombinant fusion proteins formed by a fragment (aa 286-426) of the dengue envelope protein and the P64k protein from Neisseria meningitidis. In this work we describe the immunization of Macaca fascicularis monkeys with two variants of these proteins [PD3 (insertion variant) and PD5 (fusion variant)] corresponding to serotype 2. Four doses of the proteins adjuvated in Freund's adjuvant were administered and the kinetics of antibody induction was monitored by ELISA and neutralization tests. Monkeys receiving PD3 or PD5 developed functional antibodies (Abs) in a dose-dependent manner. Following challenge with 5 log PFU of wild type dengue-2 virus (DEN2), animals immunized with PD5 were protected from developing viremia. These results constitute a proof-of-concept demonstrating that a fragment of the dengue envelope protein, containing the domain III and produced as a recombinant fusion protein in Escherichia coli, induces functional and protective immunity in a nonhuman primate model.
Hermida
Lisset
L
Center for Genetic Engineering and Biotechnology, Apdo 6162, Havana 10600, Cuba. lisset.hermida@cigb.edu.cu
Bernardo
Lídice
L
Martín
Jorge
J
Alvarez
Mayling
M
Prado
Irina
I
López
Carlos
C
Sierra
Beatriz de la C
Bde L
Martínez
Rafael
R
Rodríguez
Rosmary
R
Zulueta
Aída
A
Pérez
Ana B
AB
Lazo
Laura
L
Rosario
Delfina
D
Guillén
Gerardo
G
Guzmán
María G
MG
D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D005620:Freund's Adjuvant; D007074:Immunoglobulin G / Q000097:blood; D008252:Macaca fascicularis; D009345:Neisseria meningitidis / Q000235:genetics; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001425:Bacterial Outer Membrane Proteins; C051821:E-glycoprotein, Dengue virus type 2; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C112623:lpdA protein, Neisseria meningitidis; D005620:Freund's Adjuvant