Short-term HIV-1 treatment interruption is associated with dysregulated TLR-stimuli responsiveness

Nowroozalizadeh, Salma; Gudmundsdotter, Lindvi; Hejdeman, Bo; Andersson, Lena; Esbjörnsson, Joakim; Medstrand, Patrik; Sandström, Eric; Gaines, Hans; Wahrén, Britta; Jansson, Marianne

doi:10.4161/hv.25154

Cited by 3 publications

(3 citation statements)

References 41 publications

(48 reference statements)

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“…We noted increased TLR7/8-triggered secretion of IL-12 and IFN-α, as well as TLR9-triggered secretion of IL-12. On the other hand, we noted a reduction of TLR9 stimulated IFN-α plasmocytic and myeloid dendritic cells [ 42 ]. These results suggest that the consequences of short-term STI include dysregulated TLR responses and fluctuations in the frequencies of circulating dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy with an HIV-DNA Vaccine in Children and Adults

et al. 2014

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Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals’ immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children’s and adults’ responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4–16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected.

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Section: Discussionmentioning

confidence: 99%

Immunotherapy with an HIV-DNA Vaccine in Children and Adults

et al. 2014

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“…By contrast, studies of whole blood from HIV infected individuals on ART demonstrated reduced IFNα and IL-12 secretion in response to TLR7/8 agonists but that responsiveness was restored during treatment interruption [ 113 , 114 ]. Dhamanage et al observed that pre-exposure of pDCs to HIV reduced responsiveness to the TLR7 agonist imiquimod [ 115 ], while Pereira et al used a proteomic approach to find that pDCs and cDCs from whole blood from HIV infected donors exhibit delayed responses to several TLR ligands [ 116 ].…”

Section: Alterations To Tlr Expression and Function During Hiv Infmentioning

confidence: 99%

The Role of Toll-Like Receptors in Retroviral Infection

Browne

2020

Microorganisms

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Toll-like receptors (TLRs) are key pathogen sensing receptors that respond to diverse microbial ligands, and trigger both innate and adaptive immune responses to infection. Since their discovery, a growing body of evidence has pointed to an important role for TLRs in retroviral infection and pathogenesis. These data suggest that multiple TLRs contribute to the anti-retroviral response, and that TLR engagement by retroviruses can have complex and divergent outcomes for infection. Despite this progress, numerous questions remain about the role of TLRs in retroviral infection. In this review, I summarize existing evidence for TLR-retrovirus interactions and the functional roles these receptors play in immunity and pathogenesis, with particular focus on human immunodeficiency virus (HIV).

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“…To that end, it is fitting that among the excellent papers included in this monograph are reports on DNA vaccine strategies against these two important infections. Nowroozalizadeh et al 7 presented a paper entitled "Short-term HIV-1 treatment interruption is associated with dysregulated TLR-stimuli responsiveness." This work is summarized in their paper entitled "Electroporation mediated DNA vaccination directly to a mucosal surface results in improved immune responses."…”

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confidence: 99%