Immunogenicity of a recombinant varicella-zoster virus gE-IE63 fusion protein, a putative vaccine candidate against primary infection and zoster reactivation.
The varicella-zoster virus (VZV) envelope glycoprotein E (gE) and immediate early protein 63 (IE63) are well known targets for specific humoral and cell-mediated immune responses during VZV infection and latency, respectively. The present study evaluated the immunogenicity of an engineered chimeric recombinant gE-IE63 (recgE-IE63) protein secreted from CHO cells, wherein a soluble form of gE, deleted of its anchor and cytoplasmic domains was fused to IE63. Guinea pig vaccinations with adjuvanted recgE-IE63 elicited a strong and specific humoral immune response directed to each counterpart. Sera from recgE-IE63-immunized animals neutralized cell-free VZV. This neutralizing capacity was dependent only on the recgE moiety as serum depletions on recgE-immobilized sepharose totally abolished VZV neutralization. The cell-mediated immune response induced by recgE-IE63 was evaluated in lymphoproliferation assays. An antigen-specific proliferative response was demonstrated after lymphocyte stimulation with recIE63 but not with recgE. We conclude that recombinant chimeric recgE-IE63 induced both humoral and cell-mediated immune responses and thus could constitute a putative subunit vaccine candidate against VZV primary infection and zoster reactivation.
Jacquet
Alain
A
Department of Applied Genetics, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium. ajacquet@sga.ulb.ac.be
Haumont
Michèle
M
Massaer
Marc
M
Garcia
Lida
L
Mazzu
Pasqualina
P
Daminet
Véronique
V
Grégoire
Diane
D
Jacobs
Paul
P
Bollen
Alex
A
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001483:Base Sequence; D016466:CHO Cells; D002644:Chickenpox / Q000276:immunology / Q000517:prevention & control*; D003001:Cloning, Molecular; D006224:Cricetinae; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D006168:Guinea Pigs; D006562:Herpes Zoster / Q000276:immunology / Q000517:prevention & control*; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
D000914:Antibodies, Viral; D004274:DNA, Recombinant; D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C056913:glycoprotein E, varicella-zoster virus; C074551:immediate early protein 63, Human herpesvirus 3