TY - JOUR
T1 - A single lentivector DNA based immunization contains a late heterologous SIVmac251 mucosal challenge infection
AU - Chebloune, Yahia
AU - Moussa, Maha
AU - Arrode-Brusés, Géraldine
AU - Ronfort, Corinne
AU - Bose, Deepanwita
AU - Gagnon, Jean
AU - Gumber, Sanjeev
AU - Villinger, Tara
AU - Byrareddy, Siddappa N.
AU - Kozlowski, Pamela A.
AU - Gosse, Leslie
AU - Dereuddre-Bosquet, Nathalie
AU - Le Grand, Roger
AU - Villinger, François
N1 - Funding Information:
This work was supported by the ANRS , University Grenoble Alpes, INRA, “Investissements d’Avenir” programs managed by the ANR under reference ANR-11-INBS-0008 funding the Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France) infrastructure, and ANR-10-EQPX-02–01 funding the FlowCyTech facility (IDMIT, Fontenay-aux-Roses, France). We warmly thank all members of ASW, FlowCyTech and L2I core lab facility from IDMIT center. We also thank Antoine Blancher and Alice Aarninck (Université Paul Sabatier, CHU de Toulouse, Toulouse, France) for MHC haplotyping. We thank S. El Kennani for her assistance in figure formatting. The source of cytokines for the PHPC experiment was the Resource for Nonhuman Primate Immune Reagents (Emory University and now at UL Lafayette).
Publisher Copyright:
© 2020
PY - 2020/5/6
Y1 - 2020/5/6
N2 - Variety of conventional vaccine strategies tested against HIV-1 have failed to induce protection against HIV acquisition or durable control of viremia. Therefore, innovative strategies that can induce long lasting protective immunity against HIV chronic infection are needed. Recently, we developed an integration-defective HIV lentiDNA vaccine that undergoes a single cycle of replication in target cells in which most viral antigens are produced. A single immunization with such lentiDNA induced long-lasting T-cell and modest antibody responses in cynomolgus macaques. Here eighteen months after this single immunization, all animals were subjected to repeated low dose intra-rectal challenges with a heterologous pathogenic SIVmac251 isolate. Although the viral set point in SIVmac-infected cynomolgus is commonly lower than that seen in Indian rhesus macaques, the vaccinated group of macaques displayed a two log reduction of peak of viremia followed by a progressive and sustained control of virus replication relative to control animals. This antiviral control correlated with antigen-specific CD4+ and CD8+ T cells with high capacity of recall responses comprising effector and central memory T cells but also memory T cell precursors. This is the first description of SIV control in NHP model infected at 18 months following a single immunization with a non-integrative single cycle lentiDNA HIV vaccine. While not delivering sterilizing immunity, our single immunization strategy with a single-cycle lentivector DNA vaccine appears to provide an interesting and safe vaccine platform that warrants further exploration.
AB - Variety of conventional vaccine strategies tested against HIV-1 have failed to induce protection against HIV acquisition or durable control of viremia. Therefore, innovative strategies that can induce long lasting protective immunity against HIV chronic infection are needed. Recently, we developed an integration-defective HIV lentiDNA vaccine that undergoes a single cycle of replication in target cells in which most viral antigens are produced. A single immunization with such lentiDNA induced long-lasting T-cell and modest antibody responses in cynomolgus macaques. Here eighteen months after this single immunization, all animals were subjected to repeated low dose intra-rectal challenges with a heterologous pathogenic SIVmac251 isolate. Although the viral set point in SIVmac-infected cynomolgus is commonly lower than that seen in Indian rhesus macaques, the vaccinated group of macaques displayed a two log reduction of peak of viremia followed by a progressive and sustained control of virus replication relative to control animals. This antiviral control correlated with antigen-specific CD4+ and CD8+ T cells with high capacity of recall responses comprising effector and central memory T cells but also memory T cell precursors. This is the first description of SIV control in NHP model infected at 18 months following a single immunization with a non-integrative single cycle lentiDNA HIV vaccine. While not delivering sterilizing immunity, our single immunization strategy with a single-cycle lentivector DNA vaccine appears to provide an interesting and safe vaccine platform that warrants further exploration.
KW - CD8+ T cells
KW - Challenge
KW - HIV vaccine
KW - SIVmac251
KW - TSCM
UR - http://www.scopus.com/inward/record.url?scp=85082860350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082860350&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2020.03.053
DO - 10.1016/j.vaccine.2020.03.053
M3 - Article
C2 - 32278522
AN - SCOPUS:85082860350
SN - 0264-410X
VL - 38
SP - 3729
EP - 3739
JO - Vaccine
JF - Vaccine
IS - 21
ER -