Long-Term Central and Effector SHIV-Specific Memory T Cell Responses Elicited after a Single Immunization with a Novel Lentivector DNA Vaccine

• Type of Material: Article
• Authors: Geraldine Arrode-Bruses, Université Joseph Fourier; Maha Moussa, Université Joseph Fourier; Monique Baccard-Longere, Centre Hospitalo Universitaire de Grenoble; Francois Villinger, Emory University; Yahia Chebloune, Université Joseph Fourier
• Language: English
• Date: 2014-10-22
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Arrode-Bruses et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0110883
• Title of Journal or Parent Work: PLOS ONE
• Volume: 9
• Issue: 10
• Start Page: e110883
• End Page: e110883
• Grant/Funding Information: The work was supported by grants from Agence Nationale de Recherche sur le SIDA (ANRS, RA0000640), Institut National de Recherche Agronomique (INRA, 2012-2013-YC-DC) and Universite Joseph Fourier (UJF, AGIR 13CSV13) to YC.; GAB was financially supported by a postdoctoral fellowship from ANRS (2011-022) and Marie Curie International Reintegration Grant (IRG) program from European Commission (N° 276828- HIVNONILV, FP7-PEOPLE-2010-RG).
• Keywords: PROTECTION; IMMUNE-RESPONSES; Multidisciplinary Sciences; Science & Technology - Other Topics; HIV-1 NEF; AIDS; MAEDI-VISNA-VIRUS; ATTENUATED SIV; MAURITIAN CYNOMOLGUS; REPLICATION; RHESUS MACAQUES; Science & Technology; LIVE
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology; Biology, Virology

Abstract

Prevention of HIV acquisition and replication requires long lasting and effective immunity. Given the state of HIV vaccine development, innovative vectors and immunization strategies are urgently needed to generate safe and efficacious HIV vaccines. Here, we developed a novel lentivirus-based DNA vector that does not integrate in the host genome and undergoes a single-cycle of replication. Viral proteins are constitutively expressed under the control of Tat-independent LTR promoter from goat lentivirus. We immunized six macaques once only with CAL-SHIV-IN- DNA using combined intramuscular and intradermal injections plus electroporation. Antigen-specific T cell responses were monitored for 47 weeks post-immunization (PI). PBMCs were assessed directly ex vivo or after 6 and 12 days of in vitro culture using antigenic and/or homeostatic proliferation. IFN-γ ELISPOT was used to measure immediate cytokine secretion from antigen specific effector cells and from memory precursors with high proliferative capacity (PHPC). The memory phenotype and functions (proliferation, cytokine expression, lytic content) of specific T cells were tested using multiparametric FACS-based assays. All immunized macaques developed lasting peripheral CD8+ and CD4+ T cell responses mainly against Gag and Nef antigens. During the primary expansion phase, immediate effector cells as well as increasing numbers of proliferating cells with limited effector functions were detected which expressed markers of effector (EM) and central (CM) memory phenotypes. These responses contracted but then reemerged later in absence of antigen boost. Strong PHPC responses comprising vaccine-specific CM and EM T cells that readily expanded and acquired immediate effector functions were detected at 40/47 weeks PI. Altogether, our study demonstrated that a single immunization with a replication-limited DNA vaccine elicited persistent vaccine-specific CM and EM CD8+ and CD4+ T cells with immediate and readily inducible effector functions, in the absence of ongoing antigen expression. Copyright: