Heterologous prime-boost strategy in non-human primates combining the infective dengue virus and a recombinant protein in a formulation suitable for human use.
OBJECTIVE
The aim of the present work was to test the concept of the heterologous prime-boost strategy combining an infective dengue virus with a recombinant chimeric protein carrying domain III of the envelope protein.


METHODS
Two studies in monkeys, combining recombinant protein PD5 (domain III of the envelope protein from dengue-2 virus, fused to the protein carrier P64k) and the infective dengue virus in the same immunization schedules were carried out. Humoral and cell-mediated immunity were evaluated.


RESULTS
In the first study, monkeys received four doses of the protein PD5 and were subsequently infected with one dose of dengue virus. Antibody response measured after virus inoculation was significantly higher compared to that in non-primed monkeys and comparable to that elicited after two doses of infective virus. In a second study, monkeys were infected with one dose of the virus and subsequently boosted with one dose of the recombinant protein, reaching high levels of neutralizing antibodies, which were still detectable 14 months after the last immunization. In addition, the cellular immune response was also recalled.


CONCLUSIONS
The results obtained in the present work support the approach of heterologous prime-boosting, in either order prime or boost, combining the chimeric protein PD5 (formulated in alum-CPS-A) and an infective dengue virus. The latter could potentially be replaced by an attenuated vaccine candidate.
Valdés
Iris
I
Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, PO Box 6162, Havana 6, 10 600, Cuba. iris.valdes@cigb.edu.cu
Hermida
Lisset
L
Gil
Lázaro
L
Lazo
Laura
L
Castro
Jorge
J
Martín
Jorge
J
Bernardo
Lídice
L
López
Carlos
C
Niebla
Olivia
O
Menéndez
Tamara
T
Romero
Yaremis
Y
Sánchez
Jorge
J
Guzmán
María G
MG
Guillén
Gerardo
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D003715:Dengue / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007114:Immunization / Q000379:methods*; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001425:Bacterial Outer Membrane Proteins; D053059:Dengue Vaccines; D011994:Recombinant Proteins; C112623:lpdA protein, Neisseria meningitidis