Immunologic Control of HIV-1: What Have We Learned and Can We Induce It?

Rogan, Daniel C; Connors, Mark

doi:10.1007/s11904-021-00545-2

Cited by 7 publications

(9 citation statements)

References 97 publications

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“…From studies in humans with HIV and nonhuman primates (NHPs) with simian viruses (SIV, SHIV), potent CD8 + T-cell responses have been shown to associate with a lower viral load setpoint in both acute infection and after treatment interruption [10–14]. In elite controllers, as we will discuss, the role of HIV-specific CD8 + T-cell responses has been suggested by the association between viral control and specific enrichment of class I human or primate leukocyte antigen (HLA or Mamu) alleles and the development of potent HIV/SIV-specific CD8 + T-cell responses that are independent of the HLA/Mamu type [15–29]. More directly, depletion of CD8 + T cells has been shown to lead to viral rebound in NHPs that have either spontaneous elite control or viral suppression induced after treatment in early infection with broadly neutralizing antibodies [30 ▪ ,31–33].…”

Section: Introduction: the Role Of Cd8+ T-cell Responses In Hiv Contr...mentioning

confidence: 99%

CD8+ T-cell responses in HIV controllers: potential implications for novel HIV remission strategies

Rutishauser

Trautmann

2022

Current Opinion in HIV and AIDS

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Purpose of reviewImmunological studies of spontaneous HIV and simian virus (SIV) controllers have identified virus-specific CD8+ T cells as a key immune mechanism of viral control. The purpose of this review is to consider how knowledge about the mechanisms that are associated with CD8+ T cell control of HIV/SIV in natural infection can be harnessed in HIV remission strategies.Recent findingsWe discuss characteristics of CD8+ T-cell responses that may be critical for suppressing HIV replication in spontaneous controllers comprising HIV antigen recognition including specific human leukocyte antigen types, broadly cross-reactive T cell receptors and epitope targeting, enhanced expansion and antiviral functions, and localization of virus-specific T cells near sites of reservoir persistence. We also discuss the need to better understand the timing of CD8+ T-cell responses associated with viral control of HIV/SIV during acute infection and after treatment interruption as well as the mechanisms by which HIV/SIV-specific CD8+ T cells coordinate with other immune responses to achieve control.SummaryWe propose implications as to how this knowledge from natural infection can be applied in the design and evaluation of CD8+ T-cell-based remission strategies and offer questions to consider as these strategies target distinct CD8+ T-cell-dependent mechanisms of viral control.

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Section: Introduction: the Role Of Cd8+ T-cell Responses In Hiv Contr...mentioning

confidence: 99%

CD8+ T-cell responses in HIV controllers: potential implications for novel HIV remission strategies

Rutishauser

Trautmann

2022

Current Opinion in HIV and AIDS

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“… 14 , 15 The therapeutic vaccination platform expands and re-educates virus-specific immune responses (particularly CD8 + T - cell response) to kill infected cells before production of progeny virions. 26 This platform limits the replenishment of viral reservoirs to achieve a functional cure in the absence of ART.…”

Section: Introductionmentioning

confidence: 99%

Conserved multiepitope vaccine constructs: A potent HIV-1 therapeutic vaccine in clinical trials

Akbari

Seyedinkhorasani²,

Bolhassani

2023

The Brazilian Journal of Infectious Diseases

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“…An effective therapeutic HIV-1 vaccine should induce potent cytotoxic T cell responses which could contribute to control of viremia and thereby reduce the pool of infected cells. CD8 + T cell immune responses induced upon therapeutic vaccination during ART can contribute to control viral replication upon treatment interruption [reviewed in (6)(7)(8)(10)(11)(12)(13)].…”

Section: Introductionmentioning

confidence: 99%

Comparative immunogenicity of an mRNA/LNP and a DNA vaccine targeting HIV gag conserved elements in macaques

Valentı́n

Bergamaschi²,

Rosati³

et al. 2022

Front. Immunol.

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Immunogenicity of HIV-1 mRNA vaccine regimens was analyzed in a non-human primate animal model. Rhesus macaques immunized with mRNA in lipid nanoparticle (mRNA/LNP) formulation expressing HIV-1 Gag and Gag conserved regions (CE) as immunogens developed robust, durable antibody responses but low adaptive T-cell responses. Augmentation of the dose resulted in modest increases in vaccine-induced cellular immunity, with no difference in humoral responses. The gag mRNA/lipid nanoparticle (LNP) vaccine provided suboptimal priming of T cell responses for a heterologous DNA booster vaccination regimen. In contrast, a single immunization with gag mRNA/LNP efficiently boosted both humoral and cellular responses in macaques previously primed by a gag DNA-based vaccine. These anamnestic cellular responses were mediated by activated CD8+ T cells with a phenotype of differentiated T-bet+ cytotoxic memory T lymphocytes. The heterologous prime/boost regimens combining DNA and mRNA/LNP vaccine modalities maximized vaccine-induced cellular and humoral immune responses. Analysis of cytokine responses revealed a transient systemic signature characterized by the release of type I interferon, IL-15 and IFN-related chemokines. The pro-inflammatory status induced by the mRNA/LNP vaccine was also characterized by IL-23 and IL-6, concomitant with the release of IL-17 family of cytokines. Overall, the strong boost of cellular and humoral immunity induced by the mRNA/LNP vaccine suggests that it could be useful as a prophylactic vaccine in heterologous prime/boost modality and in immune therapeutic interventions against HIV infection or other chronic human diseases.

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Immunologic Control of HIV-1: What Have We Learned and Can We Induce It?

Cited by 7 publications

References 97 publications

CD8+ T-cell responses in HIV controllers: potential implications for novel HIV remission strategies

CD8+ T-cell responses in HIV controllers: potential implications for novel HIV remission strategies

Conserved multiepitope vaccine constructs: A potent HIV-1 therapeutic vaccine in clinical trials

Comparative immunogenicity of an mRNA/LNP and a DNA vaccine targeting HIV gag conserved elements in macaques

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