Publisher Correction: Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys

Borducchi, Erica N.; Liu, Jinyan; Nkolola, Joseph P.; Cadena, Anthony M.; Yu, Wenhan; Fischinger, Stephanie; Broge, Thomas; Abbink, Peter; Mercado, Noe B.; Chandrashekar, Abishek; Jetton, David; Peter, Lauren; McMahan, Katherine; Moseley, Edward T.; Bekerman, Elena; Hesselgesser, Joseph; Li, Wenjun; Lewis, Mark G.; Alter, Galit; Geleziunas, Romas; Barouch, Dan H.

doi:10.1038/s41586-018-0721-y

Cited by 16 publications

(16 citation statements)

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“…Though the mechanism of HIV reactivation in this study has not been fully elucidated, both latency reversal and T cell activation were dependent on type I IFNs produced through TLR7 stimulation of pDCs. Co-administration of PGT121 and Vesatolimod during ART also delayed viral rebound in SHIV-infected rhesus macaques upon ART discontinuation [190]. Finally, combined Ad26/MVA therapeutic vaccination/TLR7 stimulation was shown to increase the breadth of SIV-specific CTL responses, decrease levels of SIV DNA, and delay viral rebound following ART interruption in SIV-infected rhesus macaques [189].…”

Section: Next Generation Pharmacological Lras?mentioning

confidence: 85%

“…Among LRAs that have shown the most promise, TLR agonists have been investigated in several ex vivo and in vivo studies [188][189][190]. The TLR7 agonist GS-9620 (Vesatolimod) in combination with the HIV envelope-specific broadly neutralizing antibody (bNAb) PGT121 induced extracellular HIV-1 RNA and increased cytolytic activity in PBMCs of virally suppressed individuals [188].…”

Section: Next Generation Pharmacological Lras?mentioning

confidence: 99%

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Role of Dendritic Cells in Exposing Latent HIV-1 for the Kill

Kristoff

Rinaldo

Mailliard

2019

Viruses

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The development of effective yet nontoxic strategies to target the latent human immunodeficiency virus-1 (HIV-1) reservoir in antiretroviral therapy (ART)-suppressed individuals poses a critical barrier to a functional cure. The 'kick and kill' approach to HIV eradication entails proviral reactivation during ART, coupled with generation of cytotoxic T lymphocytes (CTLs) or other immune effectors equipped to eliminate exposed infected cells. Pharmacological latency reversal agents (LRAs) that have produced modest reductions in the latent reservoir ex vivo have not impacted levels of proviral DNA in HIV-infected individuals. An optimal cure strategy incorporates methods that facilitate sufficient antigen exposure on reactivated cells following the induction of proviral gene expression, as well as the elimination of infected targets by either polyfunctional HIV-specific CTLs or other immune-based strategies. Although conventional dendritic cells (DCs) have been used extensively for the purpose of inducing antigen-specific CTL responses in HIV-1 clinical trials, their immunotherapeutic potential as cellular LRAs has been largely ignored. In this review, we discuss the challenges associated with current HIV-1 eradication strategies, as well as the unharnessed potential of ex vivo-programmed DCs for both the 'kick and kill' of latent HIV-1.

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Section: Next Generation Pharmacological Lras?mentioning

confidence: 85%

Section: Next Generation Pharmacological Lras?mentioning

confidence: 99%

Role of Dendritic Cells in Exposing Latent HIV-1 for the Kill

Kristoff

Rinaldo

Mailliard

2019

Viruses

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“…Collectively, these novel strategies provide a platform for the optimization of the epitope targeted immunogen design approaches (97). Furthermore, advances in high throughput recombinant antibody technology has created the possibility of using bNAbs for prevention or treatment of HIV-1 infection as described above (166,167).…”

Section: Broadly Neutralizing Antibody (Bnabs) Vaccine Designmentioning

confidence: 99%

Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions

2020

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Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine; but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.

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“…RT-PCR assays were utilized to monitor viral loads, essentially as previously described (22). RNA was extracted from plasma with a QIAcube HT (Qiagen, Germany) using the QIAcube 96 Cador pathogen HT.…”

Section: Rt-qpcrmentioning

confidence: 99%

Differential Outcomes following Optimization of Simian-Human Immunodeficiency Viruses from Clades AE, B, and C

Tartaglia

Gupte

Pastores

et al. 2020

J Virol

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Simian-human immunodeficiency virus (SHIV) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (HIV-1) vaccines, therapeutics, and cure strategies. SHIVs have been optimized by incorporating HIV-1 Env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (SIV) Env to improve rhesus CD4 binding. We applied this strategy to three SHIV challenge stocks (SHIV-SF162p3, SHIV-AE16, and SHIV-325c) and observed three distinct outcomes. We constructed six Env375 variants (M, H, W, Y, F, and S) for each SHIV, and we performed a pool competition study in rhesus monkeys to define the optimal variant for each SHIV prior to generating large-scale challenge stocks. We identified SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH as the optimal variants. SHIV-SF162p3S could not be improved, as it already contained the optimal Env375 residue. SHIV-AE16W exhibited a similar replicative capacity to the parental SHIV-AE16 stock. In contrast, SHIV-325cH demonstrated a 2.6-log higher peak and 1.6-log higher setpoint viral loads than the parental SHIV-325c stock. These data demonstrate the diversity of potential outcomes following Env375 modification in SHIVs. Moreover, the clade C SHIV-325cH challenge stock may prove useful for evaluating prophylactic or therapeutic interventions against clade C HIV-1. IMPORTANCE We sought to enhance the infectivity of three SHIV stocks by optimization of a key residue in human immunodeficiency virus type 1 (HIV-1) Env (Env375). We developed the following three new simian-human immunodeficiency virus (SHIV) stocks: SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH. SHIV-SF162p3S could not be optimized, SHIV-AE16W proved comparable to the parental virus, and SHIV-325cH demonstrated markedly enhanced replicative capacity compared with the parental virus.

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Publisher Correction: Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys

Abstract: In Fig. 4b of this Article, the x-axis labels 'PGT121' and 'GS-9620' were inadvertently swapped in both graphs. In addition, in Fig. 5a and b, 'TLR7' should have been 'GS-9620' for consistency. These figures have been corrected online.

Cited by 16 publications

References 0 publications

Role of Dendritic Cells in Exposing Latent HIV-1 for the Kill

Role of Dendritic Cells in Exposing Latent HIV-1 for the Kill

Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions

Differential Outcomes following Optimization of Simian-Human Immunodeficiency Viruses from Clades AE, B, and C

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