Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection

Hahn, Patricia A.; Martins, Maurício A.

doi:10.1016/j.jve.2023.100316

Cited by 5 publications

(2 citation statements)

References 149 publications

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“…In this follow-up study, we demonstrated that PD-1-based pRhPD1-p27 DNA vaccine induced prolonged viral suppression in rhesus macaques, resulting in a survival period of more than 6 years after challenge with the CCR5-tropic, neutralization tier-2 pathogenic SHIV SF162P3CN . The viremia-free period reported here was in a similar timeframe demonstrated in the aviremic status achieved in the “Miami Monkey” that received treatment with adeno-associated viruses (AAVs) expressing three broadly neutralizing antibodies after SHIV-AD8 challenge ( 19 , 20 ). AAV-vectored neutralizing antibody delivery treatment requires the persistent presence of neutralizing antibodies to sustain viral control.…”

Section: Discussionmentioning

confidence: 56%

A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV _SF162P3CN challenge

He,

Wong,

Zhong

et al. 2023

Microbiol Spectr

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An effective vaccine for combination antiretroviral therapy (cART)-free virologic control of HIV-1 by enhancing antigen-specific effector-memory CD8 + T lymphocytes could be useful in controlling the AIDS pandemic. Previously, we demonstrated that a programmed death-1 (PD-1)-based DNA vaccine, pRhPD1-p27, was effective in inducing Gag-p27-specific effector-memory CD8 + T cells for viremia suppression in rhesus macaques infected with pathogenic SHIV SF162P3CN for 2 years. In this follow-up study, we report on two pRhPD1-p27-vaccinated and SHIV SF162P3CN -infected macaques that have remained alive to date with undetectable viremia levels and low proviral loads over 6 years in the absence of cART, achieving a state of sustained virologic control. Polyfunctional effector-memory Gag-p27-specific T cells were maintained in these macaques. Moreover, several T cell epitopes found at 6 years post-viral challenge were identical to those induced during the vaccination phase, indicating sustained vaccine-induced memory T cell responses. The viral challenge resulted in de novo Nef-specific T cell responses, which were also maintained. These Gag-p27- and Nef-specific T cell responses were stronger than those in some SHIV SF162P3CN -infected macaques that showed viremia control after experimental therapy using a tandem bispecific neutralizing antibody. Our findings indicate that the PD-1-based DNA vaccine strategy holds promise as a clinical immunotherapy for long-term HIV-1 suppression. IMPORTANCE Efficient strategies for HIV-1 cART-free virologic control are critical for ending the AIDS pandemic. The essential role of effector-memory CD8 + T cells in controlling viremia and eliminating virus-infected cells has made them a promising target for vaccine development. It has been previously reported that PD-1-based DNA vaccination was effective in inducing polyfunctional effector-memory CD8 + T cells for AIDS virus control for 2 years in rhesus monkeys. This follow-up study extends the findings and shows that a viremia-free period of over 6 years was detected in two monkeys immunized with PD-1-based DNA vaccine against pathogenic SHIV SF162P3CN infection in the absence of antiretroviral therapy. Long-term vaccine-induced memory T cell responses were detected. Our results warrant the clinical trials of PD-1-based DNA vaccines for achieving HIV-1 cART-free virologic control used either alone or in combination with other biomedical interventions.

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Section: Discussionmentioning

confidence: 56%

A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV _SF162P3CN challenge

He,

Wong,

Zhong

et al. 2023

Microbiol Spectr

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“…Various groups are studying the use of AAVs for the delivery of broadly neutralizing antibodies into skeletal muscle, to provide a long-lasting effect against HIV, either as prevention or treatment, or both. A recent review article analysed their use in HIV infection, and the current challenges and strategies that can be employed to overcome barriers to their efficacy [ 168 ].…”

Section: Hiv Gene Therapy Delivery Via Viral Vectorsmentioning

confidence: 99%

Advances in HIV Gene Therapy

Kitawi,

Ledger,

Kelleher

et al. 2024

IJMS

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Early gene therapy studies held great promise for the cure of heritable diseases, but the occurrence of various genotoxic events led to a pause in clinical trials and a more guarded approach to progress. Recent advances in genetic engineering technologies have reignited interest, leading to the approval of the first gene therapy product targeting genetic mutations in 2017. Gene therapy (GT) can be delivered either in vivo or ex vivo. An ex vivo approach to gene therapy is advantageous, as it allows for the characterization of the gene-modified cells and the selection of desired properties before patient administration. Autologous cells can also be used during this process which eliminates the possibility of immune rejection. This review highlights the various stages of ex vivo gene therapy, current research developments that have increased the efficiency and safety of this process, and a comprehensive summary of Human Immunodeficiency Virus (HIV) gene therapy studies, the majority of which have employed the ex vivo approach.

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Use of recombinant adeno-associated virus for passive immunization and protection against infectious diseases

Ryabova,

Derkaev,

Pimenov

et al. 2024

Mol. genet. mikrobiol. virusol.

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Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection

Cited by 5 publications

References 149 publications

A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV _SF162P3CN challenge

A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV _SF162P3CN challenge

Advances in HIV Gene Therapy

Use of recombinant adeno-associated virus for passive immunization and protection against infectious diseases

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Adeno-associated virus-vectored delivery of HIV biologics: the promise of a “single-shot” functional cure for HIV infection

Cited by 5 publications

References 149 publications

A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV SF162P3CN challenge

A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV SF162P3CN challenge

Advances in HIV Gene Therapy

Use of recombinant adeno-associated virus for passive immunization and protection against infectious diseases

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Product

Resources

About

A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV _SF162P3CN challenge

A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV _SF162P3CN challenge