Objective: To assess the influence of route of HIV exposure on the development of HIV-specific CD8 T-cell responses in exposed, uninfected (EU) individuals.
Design: Two groups of EU exposed to virus through either sexual or intravenous contact were studied. Group I included subjects (n = 20) who had unprotected sexual contact with known HIV-infected partners and no intravenous HIV exposure; Group II included individuals (n = 27) who had shared needles with HIV-infected partners and had no sexual exposure to this virus. Between-group comparisons were made for the proportion of responders, breadth, magnitude, and specificity of HIV-specific responses.
Methods: : The interferon-gamma ELISPOT assay was used to detect HIV-specific effector activity. Peripheral blood mononuclear cells (PBMC) from each subject were stimulated with a panel of HIV peptides restricted to the MHC class I alleles expressed by the individual.
Results: A similar proportion of EU tested from each group (35.0% Group I versus 22.2% Group II) recognized at least one HIV peptide. Group I and II subjects recognized HIV peptides with a similar cumulative intensity of 130 +/- 67.5 and 182.9 +/- 184.2 spot forming cells/1 x 10 PBMC, respectively, and similar magnitude per stimulatory peptide of 82.7 and 78.4 SFC/1 x 10 PBMC, respectively. The proportion of stimulatory peptides derived from HIV Gag, reverse transcriptase, Env, and Nef was not significantly different between the two EU groups. HLA-A*0201 restricted HIV epitopes immunodominant in infected individuals are rarely stimulatory in EU subjects.
Conclusions: Both mucosal and parenteral exposure to HIV can elicit HIV-specific CD8 T-cell responses with similar characteristics.
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Pathogens
December 2024
Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3V6, Canada.
Natural killer (NK) and CD8 T cell function is compromised in human immunodeficiency virus type 1 (HIV-1) infection by increased expression of inhibitory receptors such as TIGIT (T cell immunoreceptor with Ig and ITIM domains). Blocking inhibitory receptors or their ligands with monoclonal antibodies (mAb) has potential to improve antiviral immunity in general and facilitate HIV eradication strategies. We assessed the impact of TIGIT engagement and blockade on cytotoxicity, degranulation, and interferon-gamma (IFN-γ) production by CD8 T cells from persons living with HIV (PLWH).
View Article and Find Full Text PDFbioRxiv
December 2024
Institute of Human Virology, Departments of Pharmacology, Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
The persistence of HIV-1 reservoirs during combination anti-retroviral therapy (cART) leads to chronic immune activation and systemic inflammation in people with HIV (PWH), associating with a suboptimal immune reconstitution as well as an increased risk of non-AIDS events. This highlights the needs to develop novel therapy for HIV-1 related diseases in PWH. In this study, we assessed the therapeutic effect of CD24-Fc, a fusion protein with anti-inflammatory properties that interacts with danger-associated molecular patterns (DAMPs) and siglec-10, in chronic HIV-1 infection model using humanized mice undergoing suppressive cART.
View Article and Find Full Text PDFJ Virol
December 2024
Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
Curr Opin HIV AIDS
January 2025
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Purpose Of Review: This review focuses on the viral and immune factors influencing HIV posttreatment control (PTC), a rare condition where individuals maintain viral suppression after discontinuing antiretroviral therapy (ART).
Recent Findings: Studies demonstrate that early ART initiation leads to smaller HIV reservoirs and delayed viral rebound in PTCs. Virologically, PTCs harbor smaller HIV reservoirs and show lower levels of reservoir transcriptional activity compared with posttreatment noncontrollers.
Mol Ther Nucleic Acids
December 2024
Neuro-Aging and Viro-Immunotherapy (NAVI) Research Group, Faculty of Pharmacy and Medicine, Vrije Universiteit Brussel, Brussels, Belgium.
mRNA nanoparticles have been investigated in the context of prophylactic vaccination against HIV, but their effectivity has not been widely investigated in therapeutic vaccination. It has been suggested that a profound CD8 T cell response within lymphoid tissues, a primary site for viral reservoirs, is crucial for achieving optimal viral control, potentially correlating with protection. This study aimed to evaluate the effectiveness of mRNA lipid nanoparticles (LNPs), including a modified variant containing α-galactosylceramide as an adjuvant, termed galsomes.
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