William J. Bosche

Initial sites of SIV rebound after antiretroviral treatment cessation in rhesus macaques

Brandon F. Keele, Afam A. Okoye, Taina T. Immonen, Benjamin Varco-Merth et autres

The tissue origin(s) and the earliest viral dynamics of HIV rebound after antiretroviral therapy (ART) remain unclear. Here, using barcoded SIVmac239 in rhesus macaques (n = 24), we defined the distribution of barcode-specific viral RNA expression in tissues during ART (n = …

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Boosting SIV-specific CD8+ T cell responses prior to ART interruption extends time to SIVmac239 rebound

Were R. Omange, Benjamin Varco-Merth, Omo Fadeyi, Alejandra Marenco et autres

HIV/SIV-specific CD8+ T cell responses are typically unable to control viral rebound following antiretroviral therapy (ART) interruption (ATI). To investigate whether enhancing the magnitude and activation of SIV-specific CD8+ T cells at the time of ATI can improve the immune interception of …

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The TLR7 agonist vesatolimod does not measurably induce SIV expression in macaques receiving combination antiretroviral therapy initiated during chronic infection

Adrienne E. Swanstrom, Kelli Oswald, Randy Fast, Rebecca Shoemaker et autres

ABSTRACT Lim et al. previously reported that TLR7 agonist (Vesatolimod [VES] or the related compound GS-986) administration to SIVmac251-infected macaques receiving combination antiretroviral therapy (cART) led to transient plasma viral load (PVL) increases, viral DNA (vDNA) reductions in blood and tissues, and, …

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Identification of initial sites of SIV rebound after treatment cessation

Louis J. Picker, Brandon F. Keele, Afam A. Okoye, Taina T. Immonen et autres

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Impact of alemtuzumab-mediated lymphocyte depletion on SIV reservoir establishment and persistence

Benjamin Varco-Merth, Morgan Chaunzwa, Derick M. Duell, Alejandra Marenco et autres

Persistence of the rebound-competent viral reservoir (RCVR) within the CD4+ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected …

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Early antiretroviral therapy in SIV-infected rhesus macaques reveals a multiphasic, saturable dynamic accumulation of the rebound competent viral reservoir

Brandon F. Keele, Afam A. Okoye, Christine M. Fennessey, Benjamin Varco-Merth et autres

The rebound competent viral reservoir (RCVR)-virus that persists during antiretroviral treatment (ART) and can reignite systemic infection when treatment is stopped-is the primary barrier to eradicating HIV. We used time to initiation of ART during primary infection of rhesus macaques (RMs) after …

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Myeloid cell tropism enables MHC-E–restricted CD8 + T cell priming and vaccine efficacy by the RhCMV/SIV vaccine

Scott G. Hansen, Meaghan H. Hancock, Daniel Malouli, Emily E. Marshall et autres

The strain 68-1 rhesus cytomegalovirus (RhCMV)–based vaccine for simian immunodeficiency virus (SIV) can stringently protect rhesus macaques (RMs) from SIV challenge by arresting viral replication early in primary infection. This vaccine elicits unconventional SIV-specific CD8 + T cells that recognize epitopes presented …

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RhCMV/SIV tropism modulation programs unconventional CD8+ T cell priming and vaccine efficacy

Meaghan H. Hancock, Scott G. Hansen, Daniel Malouli, Emily E. Marshall et autres

Abstract Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens demonstrate a vaccine efficacy where 50–60% of vaccinated rhesus macaques are protected from SIV challenge. Intriguingly, RhCMV/SIV vectors elicit CD8+ T cells recognizing epitopes presented by MHC-II and MHC-E …

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Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy

Fredrik Barrenäs, Scott G. Hansen, G. Lynn Law, Connor Driscoll et autres

Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68-1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no …

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Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy

Marieke C. Verweij, Scott G. Hansen, Ravi Iyer, Nessy John et autres

Viral peptide is key to T cell priming Simian immunodeficiency virus (SIV) vaccines containing a strain 68-1 rhesus cytomegalovirus (RhCMV) vector elicit strong CD8 + T cell responses that can control and clear SIV infections. The SIV peptides targeted by these T …

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Cytomegaloviral determinants of CD8 + T cell programming and RhCMV/SIV vaccine efficacy

Daniel Malouli, Scott G. Hansen, Meaghan H. Hancock, Colette M. Hughes et autres

T cell responses as mediators of anti-SIV efficacy and indicate that translation of RhCMV/SIV vector efficacy to humans will likely require deletion of all genes that inhibit these responses from the HCMV/HIV vector.

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Antibody-mediated depletion of viral reservoirs is limited in SIV-infected macaques treated early with antiretroviral therapy

Adrienne E. Swanstrom, Taina T. Immonen, Kelli Oswald, Cathi Pyle et autres

The effectiveness of virus-specific strategies, including administered HIV-specific mAbs, to target cells that persistently harbor latent, rebound-competent HIV genomes during combination antiretroviral therapy (cART) has been limited by inefficient induction of viral protein expression. To examine antibody-mediated viral reservoir targeting without a …

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