Immunological evaluation in nonhuman primates of formulations based on the chimeric protein P64k-domain III of dengue 2 and two components of Neisseria meningitidis.
The main problem in the development of successful vaccines against dengue based on recombinant proteins is the necessity to use potent adjuvants to reach a proper functional immune response. Our group reported the expression, characterization and immunological evaluation of the recombinant protein PD5, which contains the domain III of the Envelope protein from dengue 2 virus fused to the carrier protein P64k. This construct completely protected monkeys against viral challenge when the Freund's adjuvant was employed. Therefore, to define suitable formulations for human use, the present work relies on the evaluation of PD5, produced with a high purity and under GMP conditions, when formulated either with outer membrane vesicles (OMV) or the serogroup A capsular polysaccharide (CPS-A) from Neisseria meningitidis, both adsorbed on aluminium hydroxide. The antibody response to the formulation containing the CPS-A was clearly superior to that of the formulation with OMV. The experiment of in vivo protection supported this evidence, since only the group immunized with PD5 and CPS-A was partially protected upon viral challenge. This is the first study in which the polysaccharide A of N. meningitidis is successfully employed as adjuvant for viral antigens.
Valdés
Iris
I
Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba. iris.valdes@cigb.edu.cu
Hermida
Lisset
L
Martín
Jorge
J
Menéndez
Tamara
T
Gil
Lázaro
L
Lazo
Laura
L
Castro
Jorge
J
Niebla
Olivia
O
López
Carlos
C
Bernardo
Lídice
L
Sánchez
Jorge
J
Romero
Yaremis
Y
Martínez
Rafael
R
Guzmán
María G
MG
Guillén
Gerardo
G
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D003715:Dengue / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D022142:Secretory Vesicles / Q000276:immunology; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D053059:Dengue Vaccines; C051821:E-glycoprotein, Dengue virus type 2; D011135:Polysaccharides, Bacterial; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D000536:Aluminum Hydroxide