Therapeutic vaccination against HIV: current progress and future possibilities

Although effective in reducing mortality, current antiretroviral therapy for HIV infection involves complex and expensive drug regimens that are toxic and difficult to take. Eradication of HIV reservoirs is not possible with existing therapies. The concept of therapeutic vaccination has been investigated to increase the potency and breadth of anti-HIV immune responses in order to delay or reduce antiretroviral therapy use. A variety of approaches targeted to both cell- and antibody-mediated immunity have been developed, including whole inactivated HIV-1, protein subunits and synthetic peptides, DNA vaccines and a number of viral vectors expressing HIV-1. These investigations have occurred in the absence of a clear understanding of disease pathogenesis or the correlates of protective immunity. At this time, there is no licensed therapeutic vaccine for any viral disease, including HIV; however, this review will consider recent progress in the field and summarize the challenges faced in the development of a therapeutic HIV vaccine.

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Plasmacytoid Dendritic Cells Impair Anti-HIV Immunity and HIV-1 Persistence During Antiretroviral Therapy Via IDO-Dependent Mechanisms

SSRN Electronic Journal ◽

10.2139/ssrn.3471314 ◽

2019 ◽

Author(s):

Guangming Li ◽

Jianping Ma ◽

Haisheng Yu ◽

Wenwen Bi ◽

Xuguang Zhai ◽

...

Keyword(s):

Dendritic Cells ◽

Antiretroviral Therapy ◽

Plasmacytoid Dendritic Cells ◽

Anti Hiv ◽

Hiv 1

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REVIEW OF HIV MODELS: THE ROLE OF THE NATURAL IMMUNE RESPONSE AND IMPLICATIONS FOR TREATMENT

Journal of Biological System ◽

10.1142/s0218339004001099 ◽

2004 ◽

Vol 12 (02) ◽

pp. 123-135 ◽

Cited By ~ 4

Author(s):

REBECCA V. CULSHAW

Keyword(s):

Immune Response ◽

Optimal Treatment ◽

Minimal Cost ◽

Treatment Scenario ◽

Forcing Function ◽

Drug Regimens ◽

Differential Equations Models ◽

Anti Hiv ◽

Hiv 1

We present a review and comparison of several recent differential equations models of treatment of HIV-1 infection. We seek to clarify the role of the natural anti-HIV immune response and determine its effect upon optimal treatment schemes. In this paper, we consider systems in which treatment is expressed as a forcing function, as well as those in which we determine optimal treatment via control theoretic techniques. The primary goal of this study is to compare treatment schemes for systems in which a natural nonconstant immune response of the patient is considered explicitly with those that consider implicitly a constant non-specific immune response. We find that when the natural immune response can be boosted sufficiently, drug levels may not need to be as high as previously supposed. This implies that a treatment scenario in which intervals of drug treatment are alternated with some form of immune-boosting therapy may be highly beneficial in terms of reducing toxicity to the patient. Additionally, in developing countries where HIV infection is widespread and sufficient funds are not available to supply rigourous drug regimens, the implications of these models are profound, as they suggest methods of treating HIV at a minimal cost.

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Restoration of Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Responses in CD8+ T Cells from Late-Stage Patients on Prolonged Antiretroviral Therapy by Stimulation In Vitro with HIV-1 Protein-Loaded Dendritic Cells

Journal of Virology ◽

10.1128/jvi.75.9.4413-4419.2001 ◽

2001 ◽

Vol 75 (9) ◽

pp. 4413-4419 ◽

Cited By ~ 26

Author(s):

Zheng Fan ◽

Xiao-Li Huang ◽

Luann Borowski ◽

John W. Mellors ◽

Charles R. Rinaldo

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Dendritic Cells ◽

Antiretroviral Therapy ◽

Immunodeficiency Virus ◽

Ifn Γ ◽

Anti Hiv ◽

Hiv 1

ABSTRACT We demonstrate that dendritic cells loaded in vitro with human immunodeficiency virus type 1 (HIV-1) protein-liposome complexes activate HLA class I-restricted anti-HIV-1 cytotoxic T-lymphocyte and gamma interferon (IFN-γ) responses in autologous CD8+ T cells from late-stage HIV-1-infected patients on prolonged combination drug therapy. Interleukin-12 enhanced this effect through an interleukin-2- and IFN-γ-mediated pathway. This suggests that dendritic cells from HIV-1-infected persons can be engineered to evoke stronger anti-HIV-1 CD8+ T-cell reactivity as a strategy to augment antiretroviral therapy.

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Clinical Pharmacology in HIV Therapy

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.02240218 ◽

2018 ◽

Vol 14 (3) ◽

pp. 435-444 ◽

Cited By ~ 11

Author(s):

Mohamed G. Atta ◽

Sophie De Seigneux ◽

Gregory M. Lucas

Keyword(s):

Antiretroviral Therapy ◽

Morbidity And Mortality ◽

Combination Antiretroviral Therapy ◽

Access To Treatment ◽

Hiv Therapy ◽

Antiretroviral Drug ◽

Treatment Morbidity ◽

Drug Regimens ◽

Hiv 1

The success of combination antiretroviral therapy in the treatment of HIV-1–positive individuals has shifted clinical attention toward combination antiretroviral drug regimens that optimize tolerability, long-term safety, and durable efficacy. Wherever patients have access to treatment, morbidity and mortality are increasingly driven by non–HIV-associated comorbidities, which may be observed earlier than in age-matched controls and despite the best available combination antiretroviral therapy. Similarly, HIV-1–positive individuals are now diagnosed and treated earlier with anticipated lifelong therapy. The contribution of specific antiretroviral agents to long-term morbidity and mortality is dependent on the pharmacologic characteristics of these agents, and it is increasingly important in this context.

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A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy

Vaccine ◽

10.1016/j.vaccine.2016.03.021 ◽

2016 ◽

Vol 34 (19) ◽

pp. 2225-2232 ◽

Cited By ~ 14

Author(s):

Frank Y. Tung ◽

Jack K. Tung ◽

Suresh Pallikkuth ◽

Savita Pahwa ◽

Margaret A. Fischl

Keyword(s):

Antiretroviral Therapy ◽

Immune Responses ◽

Highly Active Antiretroviral Therapy ◽

Highly Active ◽

Anti Hiv ◽

Hiv 1

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Impact of highly active antiretroviral therapy on the maturation of anti-HIV-1 antibodies during primary HIV-1 infection

HIV Medicine ◽

10.1111/j.1468-1293.2006.00406.x ◽

2006 ◽

Vol 7 (8) ◽

pp. 514-519 ◽

Cited By ~ 14

Author(s):

L Adalid-Peralta ◽

L Grangeot-Keros ◽

A Rudent ◽

N Ngo-Giang-Huong ◽

R Krzysiek ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Highly Active ◽

Anti Hiv ◽

Hiv 1

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A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy

Vaccine ◽

10.1016/j.vaccine.2009.05.016 ◽

2009 ◽

Vol 27 (43) ◽

pp. 6088-6094 ◽

Cited By ~ 61

Author(s):

Rajesh T. Gandhi ◽

David O’Neill ◽

Ronald J. Bosch ◽

Ellen S. Chan ◽

R. Pat Bucy ◽

...

Keyword(s):

Dendritic Cells ◽

Antiretroviral Therapy ◽

Vaccine Trial ◽

Therapeutic Vaccine ◽

Hiv 1

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Phylogenetic analysis of HIV-1 archived DNA in blood and gut-associated lymphoid tissue in two patients under antiretroviral therapy

Gut Pathogens ◽

10.1186/s13099-021-00416-6 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Patricia Recordon-Pinson ◽

Annie Gosselin ◽

Petronela Ancuta ◽

Jean-Pierre Routy ◽

Hervé Fleury

Keyword(s):

Antiretroviral Therapy ◽

Genome Sequencing ◽

Dna Sequences ◽

Lymphoid Tissue ◽

Mononuclear Cells ◽

Therapeutic Vaccine ◽

Sequencing Analysis ◽

Proviral Dna ◽

Single Genome ◽

Hiv 1

AbstractOne of the approaches to cure human immunodeficiency virus (HIV) is the use of therapeutic vaccination. We have launched the Provir/Latitude 45 study to identify conserved CTL epitopes in archived HIV-1 DNA according to the HLA class I alleles in aviremic patients under antiretroviral therapy (ART). A HIV-1 polypeptidic therapeutic vaccine based on viral sequence data obtained from circulating blood was proposed; here, our aim was to compare the proviral DNA in blood and gut-associated lymphoid tissue (GALT). Peripheral blood mononuclear cells and gut biopsies were obtained from two HIV-1 infected patients under successful antiretroviral therapy. Total DNA was extracted including the proviral DNA. The HIV-1 reverse transcriptase was sequenced in both compartments using next generation sequencing followed by single genome sequencing; phylogenetic trees were established and compared. The proviral sequences of both compartments intra-patient exhibited a very low genetic divergence while it was possible to differentiate the sequences inter-patients; single genome sequencing analysis of two couples of samples confirmed that there was no compartmentalization of the sequences intra-patient. We conclude that, considering these two cases, the proviral DNA sequences in blood and GALT are similar and that the epitope analysis of HIV-1 provirus in blood should be considered as relevant to that observed in the GALT, a hard-to-reach major compartment, and can therefore be used for therapeutic vaccine approaches.

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Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

10.1101/324509 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yehuda Z. Cohen ◽

Julio C. C. Lorenzi ◽

Lisa Krassnig ◽

John P. Barton ◽

Leah Burke ◽

...

Keyword(s):

Clinical Trial ◽

Antiretroviral Therapy ◽

Dominant Species ◽

Treatment Interruption ◽

Latent Reservoir ◽

Analytical Treatment ◽

Quantitative Changes ◽

Anti Hiv ◽

Hiv 1 ◽

Amino Acid Variants

AbstractA clinical trial was performed to evaluate 3BNC117, a potent anti_HIV_1 antibody, in infected individuals during suppressive antiretroviral therapy (ART) and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative outgrowth assay (Q2VOA) at entry and after 6 months, prior to ATI. Although there were no significant quantitative changes in the size of the reservoir, the composition of circulating reservoir clones varied over the 6_month period before treatment interruption in a manner that did not correlate with antibody sensitivity. The neutralization profile obtained from the reservoir by Q2VOA was predictive of time to rebound after ATI, and thus of antibody efficacy. Although 3BNC117 binding site amino acid variants found in rebound viruses pre_existed in the latent reservoir, only 3 of 217 rebound viruses were identical to 868 latent viruses. Instead many of the rebound viruses appeared to be recombinants, even in individuals with resistant reservoir viruses. By incorporating the possibility of recombination, 63% of the rebound viruses could have derived from the observed latent reservoir. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating reservoir, but instead appear to represent recombinants.SummaryIn the setting of a clinical trial evaluating the anti_HIV_1 antibody 3BNC117, Cohen et al. demonstrate that rebound viruses that emerge following interruption of antiretroviral therapy are distinct from circulating latent viruses. However, rebound viruses often appear to be recombinants between isolated latent viruses.

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