Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4×: a phase 2 randomised, double-blind, placebo-controlled trial

Pollard, Richard B.; Rockstroh, Jürgen K.; Pantaleo, Giuseppe; Asmuth, David M.; Peters, Barry; Lazzarin, Adriano; García, Felipe; Ellefsen, Kim; Podzamczer, Daniel; Lunzen, Jan van; Arastéh, Keikawus; Schürmann, Dirk; Clotet, Bonaventura; Hardy, William; Mitsuyasu, Ronald T.; Moyle, Graeme; Plettenberg, Andreas; Fisher, Martin; Fätkenheuer, Gerd; Fischl, Margaret A.; Taiwo, Babafemi; Baksaas, Ingebjørg; Jolliffe, Darren; Persson, Stefan; Jelmert, Øyvind; Hovden, Arnt Ove; Sommerfelt, Maja A.; Wendel-Hansen, Vidar; Sørensen, Birger

doi:10.1016/s1473-3099(13)70343-8

Cited by 94 publications

(76 citation statements)

References 37 publications

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“…Moreover three patients had a prolonged period of treatment interruption during which stable CD4 counts and low viral loads were maintained. Although this trial did not have a similar ATI period in the placebo group, the observed median virus load at the end of the 12-week ATI was lower in the vaccinated group (3.45 log 10 copies/ml) in comparison to the placebo groups in prior therapeutic HIV vaccine trials [7,8]. Both of these studies had similar recruitment criteria and trial design as the current study.…”

Section: Discussionmentioning

confidence: 77%

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

Tung

Pallikkuth

et al. 2016

Vaccine

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Section: Discussionmentioning

confidence: 77%

“…Although some studies have suggested that immunization might affect viral control in vivo, these studies generally have been modest and at the limits of biological significance [7][8][9][10][11][12][13][14][15][16]. There are a number of reasons why HIVAX could be more potent in enhancing HIV-1 specific T cell response.…”

Section: Discussionmentioning

confidence: 99%

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

Tung

Pallikkuth

et al. 2016

Vaccine

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“…A number of potential therapeutic vaccines have improved anti-HIV-1 immune responses in vivo (17)(18)(19)(20) or delayed viral rebound during ATI in a macaque model (21) and could theoretically be administered prior to latency reversal to prime the immune system for killing of reactivated cells. A recent trial examined the combined effects of administering the therapeutic vaccine Vacc-4x (22) and granulocyte-macrophage colony-stimulating factor (GM-CSF) along with the LRA romidepsin (23). While a decrease in total HIV-1 DNA after immunization and romidepsin treatment could be detected, this combined "prime and shock" strategy was unable to prevent viral rebound after the interruption of ART.…”

Section: Discussionmentioning

confidence: 99%

Anti-HIV-1 ADCC Antibodies following Latency Reversal and Treatment Interruption

Lee

Kristensen

Rasmussen

et al. 2017

J Virol

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There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We found that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI), 21 to 59 days, was not sufficient to stimulate an increase in ADCC-competent antibodies, despite viral rebound in all subjects who underwent the short ATI. In contrast, a longer ATI, 2 to 12 months, among subjects enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro. These results show that there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies toward eliminating latently infected cells.IMPORTANCE The "shock and kill" HIV-1 cure strategy aims to reactivate HIV-1 expression in latently infected cells and subsequently eliminate the reactivated cells through immune-mediated killing. Several latency reversing agents (LRAs) have been examined in vivo, but LRAs alone have not been able to achieve HIV-1 remission and prevent viral rebound following analytical treatment interruption (ATI). In this study, we examined whether LRA treatment or ATI can provide sufficient antigenic stimulus to boost HIV-1-specific functional antibodies that can eliminate HIV-1-infected cells. Our study has implications for the antigenic stimulus required for antilatency strategies and/or therapeutic vaccines to boost functional antibodies and assist in eliminating the latent reservoir.

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“…in addition to the above methods, there are the immune intervention [37] , directly killing virus [38] , development of vaccine [39] and so on . [12].…”

Section: Discussionmentioning

confidence: 99%

The Research Progress of the Fuctional Cure of AIDS

Xu¹,

Luo²

2015

J. Appl. Virol.

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Acquired Immune Deficiency Syndrome remains incurable even though it has been more than thirty years since first discovered in 1981. Highly Active Anti-retroviral Therapy provides effective treatment to AIDS patients. However, Human Immunodeficiency Virus will rebound due to the existence of the latent viral reservoir if Active Anti-retroviral Therapy (ART) interrupted. Functional cure refers to keep viral load at low or undetectable level (at least for a certain period of time) after interrupting antiretroviral treatment. This brief review focuses on the achievement in functional cure of AIDS.

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Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4×: a phase 2 randomised, double-blind, placebo-controlled trial

Cited by 94 publications

References 37 publications

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

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

Anti-HIV-1 ADCC Antibodies following Latency Reversal and Treatment Interruption

The Research Progress of the Fuctional Cure of AIDS

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