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The HIV/AIDS vaccine candidate MVA-B administered as a single immunogen in humans triggers robust, polyfunctional, and selective effector memory T cell responses to HIV-1 antigens.

Authors :
Gómez CE
Nájera JL
Perdiguero B
García-Arriaza J
Sorzano CO
Jiménez V
González-Sanz R
Jiménez JL
Muñoz-Fernández MA
López Bernaldo de Quirós JC
Guardo AC
García F
Gatell JM
Plana M
Esteban M
Source :
Journal of virology [J Virol] 2011 Nov; Vol. 85 (21), pp. 11468-78. Date of Electronic Publication: 2011 Aug 24.
Publication Year :
2011

Abstract

Attenuated poxvirus vectors expressing human immunodeficiency virus type 1 (HIV-1) antigens are considered promising HIV/AIDS vaccine candidates. Here, we describe the nature of T cell immune responses induced in healthy volunteers participating in a phase I clinical trial in Spain after intramuscular administration of three doses of the recombinant MVA-B-expressing monomeric gp120 and the fused Gag-Pol-Nef (GPN) polyprotein of clade B. The majority (92.3%) of the volunteers immunized had a positive specific T cell response at any time postvaccination as detected by gamma interferon (IFN-γ) intracellular cytokine staining (ICS) assay. The CD4(+) T cell responses were predominantly Env directed, whereas the CD8(+) T cell responses were similarly distributed against Env, Gag, and GPN. The proportion of responders after two doses of MVA-B was similar to that obtained after the third dose of MVA-B vaccination, and the responses were sustained (84.6% at week 48). Vaccine-induced CD8(+) T cells to HIV-1 antigens after 1 year were polyfunctional and distributed mainly within the effector memory (TEM) and terminally differentiated effector memory (TEMRA) T cell populations. Antivector T cell responses were mostly induced by CD8(+) T cells, highly polyfunctional, and of TEMRA phenotype. These findings demonstrate that the poxvirus MVA-B vaccine candidate given alone is highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4 and CD8 T cell responses to HIV-1 antigens, with preference for TEM. Thus, on the basis of the immune profile of MVA-B in humans, this immunogen can be considered a promising HIV/AIDS vaccine candidate.

Details

Language :
English
ISSN :
1098-5514
Volume :
85
Issue :
21
Database :
MEDLINE
Journal :
Journal of virology
Publication Type :
Academic Journal
Accession number :
21865377
Full Text :
https://doi.org/10.1128/JVI.05165-11