Early Env-specific CTLs effectively suppress viral replication in SHIV controller macaques

Jin, Fan; Liang, Hua; Shen, Tao; Wang, Shuo; Ji, Xiaolin; Yee, Cassian; Lu, Fengmin; Shao, Yiming

doi:10.1016/j.cellimm.2018.05.001

Cited by 4 publications

(6 citation statements)

References 28 publications

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“…This protection can be related to the correlation that we observed between T-cell-specific responses and viremia control. The protective role of cellular immune responses has already been described in primates exposed to SHIV challenges 44 , 45 or in humans infected with HIV-1 46 . Although we did not find a correlation between vaccine antibody titers and viral load levels, we cannot exclude that they contributed to the control of viremia, as previously shown in NHP-infection model through viral entry neutralization or antibody-dependent cytotoxicity/phagocytosis mechanisms 47 , 48 .…”

Section: Discussionmentioning

confidence: 93%

A recombinant measles virus vaccine strongly reduces SHIV viremia and virus reservoir establishment in macaques

et al. 2021

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Replicative vectors derived from live-attenuated measles virus (MV) carrying additional non-measles vaccine antigens have long demonstrated safety and immunogenicity in humans despite pre-existing immunity to measles. Here, we report the vaccination of cynomolgus macaques with MV replicative vectors expressing simian-human immunodeficiency virus Gag, Env, and Nef antigens (MV-SHIV Wt) either wild type or mutated in the immunosuppressive (IS) domains of Nef and Env antigens (MV-SHIV Mt). We found that the inactivation of Nef and Env IS domains by targeted mutations led to the induction of significantly enhanced post-prime cellular immune responses. After repeated challenges with low doses of SHIV-SF162p3, vaccinees were protected against high viremia, resulting in a 2-Log reduction in peak viremia, accelerated viral clearance, and a decrease -even complete protection for nearly half of the monkeys- in reservoir cell infection. This study demonstrates the potential of a replicative viral vector derived from the safe and widely used measles vaccine in the development of a future human vaccine against HIV-1.

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Section: Discussionmentioning

confidence: 93%

A recombinant measles virus vaccine strongly reduces SHIV viremia and virus reservoir establishment in macaques

et al. 2021

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“…After three rounds of stimulation, an aliquot of 100,000 cells from each well was co-cultured overnight with peptide-pulsed K562 cells at a ratio of 10 : 1 to assay for antigen specific T cells using flow cytometry-based intracellular IFN-γ production assay 78 . The cells were cultured in the presence of the intracellular protein transport inhibitor Brefeldin A (Thermo Fisher, USA).…”

Section: Methodsmentioning

confidence: 99%

Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma

et al. 2020

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Complex tumor microenvironmental (TME) features influence the outcome of cancer immunotherapy (IO). Here we perform immunogenomic analyses on 67 intratumor subregions of a PD-1 inhibitor-resistant melanoma tumor and 2 additional metastases arising over 8 years, to characterize TME interactions. We identify spatially distinct evolution of copy number alterations influencing local immune composition. Sub-regions with chromosome 7 gain display a relative lack of leukocyte infiltrate but evidence of neutrophil activation, recapitulated in The Cancer Genome Atlas (TCGA) samples, and associated with lack of response to IO across three clinical cohorts. Whether neutrophil activation represents cause or consequence of local tumor necrosis requires further study. Analyses of T-cell clonotypes reveal the presence of recurrent priming events manifesting in a dominant T-cell clonotype over many years. Our findings highlight the links between marked levels of genomic and immune heterogeneity within the physical space of a tumor, with implications for biomarker evaluation and immunotherapy response.

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“…Rhesus macaque PBMCs were isolated from EDTA-treated venous blood by Ficoll Hypaque centrifugation (Sigma) within 6 h of collection. After cell counting, PBMCs were resuspended in R10 medium (RPMI-1640 medium supplemented with 10% FBS, 2 mmol L-glutamine, 25 mM HEPES, 100 U/ml penicillin, 100 mg/ml streptomycin) for next experiments 18 .…”

Section: Methodsmentioning

confidence: 99%

“…Initial gating was performed with a forward scatter (area) versus side scatter (area) lymphocyte gate. CD4 and CD8 cells consisted of live (viability stain negative) CD3 + T cells 18 . In Fig.…”

Section: Methodsmentioning

confidence: 99%

“…CD4 + T-cells were isolated from PBMCs by positive selection (Miltenyi Biotec, Catalogue# 130-092-144) and activated with 5 μg/ml Phytohemagglutinin-L (PHA-L, Sigma, Catalogue# L2769) and 100 IU/ml IL-2 (PeproTech, Catalogue# 200–02) for three days and then infected with SHIV-SF162P3 at a multiplicity of infection of 0.01 18 . After 4 h of incubation with the virus, infected cells were washed twice and resuspended at R10 medium with IL-2 (50 IU/ml) and were cultured in triplicate in 96-well plates at 10 5 cells/well, alone (positive control) or together with autologous CTL-lines at an effector-to- target ratio of 1:1, 2:1 and 5:1.…”

Section: Methodsmentioning

confidence: 99%

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CTL-mediated immunotherapy can suppress SHIV rebound in ART-free macaques

Jin

Liang

et al. 2019

Nat Commun

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A major barrier to human immunodeficiency virus (HIV) cure is the existence of viral reservoirs that lead to viral rebound following discontinuation of antiretroviral therapy (ART). We postulate that enhancing cytotoxic T lymphocytes (CTL) targeting conserved envelope (Env) regions can eliminate HIV infected cells in latency. Here, we evaluate the use of adoptively transferred HIV vaccine-induced subtype C Env-specific CTLs in a macaque subtype B simian-human immunodeficiency virus (SHIV) model to determine whether plasma viremia can be controlled after ART interruption. We demonstrate that adoptive cellular therapy (ACT) using autologous Env-specific T cells augmented by therapeutic vaccination can suppress ART-free viral rebound in the SHIV model. Furthermore, phenotypic and functional characterization of adoptively transferred cells in ACT-responsive and nonresponsive animals support a critical role for cross-reactive central memory T cells in viremia control. Our study offers an approach to potentiate immunological suppression of HIV in the absence of antiviral drugs.

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Early Env-specific CTLs effectively suppress viral replication in SHIV controller macaques

Cited by 4 publications

References 28 publications

A recombinant measles virus vaccine strongly reduces SHIV viremia and virus reservoir establishment in macaques

A recombinant measles virus vaccine strongly reduces SHIV viremia and virus reservoir establishment in macaques

Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma

CTL-mediated immunotherapy can suppress SHIV rebound in ART-free macaques

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