Current HIV Research - Online First
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Current Approaches for Assessments of Neutralizing, Binding, and Effector Functions of Antibodies on the Path to Antibody-Mediated Prevention Strategies for HIV-1
Available online: 27 March 2025More LessRobust assay technologies and reference reagents are essential components in efforts to develop safe and effective antibody-mediated prevention strategies for HIV-1. Here, we describe current approaches used to conduct standardized assessments of neutralizing, binding, and Fc receptor-mediated effector functions of vaccine-elicited antibodies, with an emphasis on recent developments that enable early precursors and intermediates of broadly neutralizing antibodies (bnAbs) to be monitored. We also describe how these assay technologies were adapted to facilitate clinical evaluations of passively delivered bnAbs for HIV-1 prevention.
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Fc Functions and Anti-HIV Neutralizing Antibodies: A Perspective
Authors: Hillary A Vanderven and Stephen J KentAvailable online: 25 March 2025More LessControversy exists around the relative merits of Fc functions in controlling or preventing HIV-1 infection. Proponents point to general correlations of Fc functions with control of HIV, indicating that non-neutralizing antibodies could force immune escape, as observed in the early experiments with Fc mutants of the b12-neutralizing monoclonal antibody. Nay-sayers point to the primary role of neutralization in the control of HIV, the general failure of vaccine trials including antibodies with Fc functions, and the lack of additional benefit with newer broadly neutralizing Ab, such as PGT121. The truth may lie somewhere in between and there are lessons to be learned from the utility of Fc functions in other viral infections. In general, however, the additional benefit of Fc function over and above robust anti-HIV neutralizing antibodies may be modest. The intense primary research focus on delivering and inducing potent and broadly neutralizing antibodies, regardless of their Fc function potential, is justified.
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The Germline Targeting Vaccine Concept: Overview and Updates from HIV Pre-Clinical and Clinical Trials
Available online: 21 February 2025More LessAn effective HIV-1 vaccine should elicit diverse immune responses, including broadly neutralizing antibodies (bNAbs). Such antibodies recognize regions of the viral envelope glycoprotein (Env) that are conserved among the diverse HIV-1 clades and strains. They are isolated from people living with HIV-1 to protect animals from experimental viral exposure and reduce HIV-1 acquisition in clinical settings. However, despite efforts spanning several decades, bNAbs have not been elicited through immunization. The HIV Env efficiently binds bNAbs, but not their unmutated (germline, gl) precursors. In contrast, Env readily engages the germline precursors of antibodies with no, or very narrow, cross-neutralizing activities (non-neutralizing antibodies, nnAbs). That, in part, explains why Env-based immunogens consistently elicit nnAbs, but not bNAbs. In the past decade, Env-derived proteins have been specifically designed to engage the germline precursors of diverse bNAbs. These ‘germline-targeting’ Env immunogens activate the corresponding naive B cells in vivo, but are unable to guide their proper maturation towards their broadly neutralizing forms. For this, immunizations with currently not well-defined heterologous Envs are required. Here, we discuss the development of germline-targeting Env immunogens, their in vivo evaluation, and the strategies currently under evaluation that aim to rapidly guide the maturation of germline-precursor BCRs into their broadly neutralizing forms.
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The Characteristics of Peripheral Blood Lymphocyte Subsets in HIV-related Diffuse Large B-cell Lymphoma Patients and Their Impact on Treatment Efficacy
Authors: Huiyu Xiang, Can Lin, Shuang Chen, Yu Peng, Tingting Jiang, Changhai Lin, Qing Xiao, Xiaomei Zhang, Tingting Liu, Nanjun Li, Xinyi Tang, Yakun Zhang, Junxi Liu and Zailin YangAvailable online: INVALID DATEMore LessIntroductionPeripheral blood lymphocyte subsets have been shown to influence prognosis in HIV-associated Diffuse Large B-Cell Lymphoma (HIV-DLBCL), a rare and highly aggressive form of non-Hodgkin's lymphoma linked to immunosuppression and abnormal B-cell proliferation. To lay the foundation for individualized therapy based on factors such as CD4+/CD8+ ratio and Treg/NK cell characteristics, this retrospective study was conducted to explore the variations in lymphocyte subset levels.
MethodsOverall, 51 HIV-DLBCL patients, 50 DLBCL patients, and 42 Healthy Donors (HD) were enrolled in the study. Data were extracted from outpatient records and the Hospital Information Management System. SPSS 27.0 software was used for statistical analysis of the data.
ResultsSignificant differences in lymphocyte subsets were observed between groups. HIV-DLBCL patients showed decreased CD4+ T cell and regulatory T cell (Treg) counts/percentages compared to DLBCL patients and HD, but increased CD8+ T cell counts and percentages, as well as Treg percentages. Age-stratified analysis revealed that older HIV-DLBCL patients had lower CD8+ T cell counts, reduced CD3+ T cell percentages, and elevated CD56+CD16+ NK cell proportions compared to their younger counterparts.
DiscussionThis study revealed a distinct pattern of immune dysregulation in HIV-DLBCL patients, characterized by CD4+ T cell depletion and CD8+ T cell expansion, which is consistent with previous studies. Age-related immunosenescence may exacerbate the increased proportion of NK cells and the decline in T-cell function, suggesting a poorer prognosis in elderly patients. However, the lack of association between lymphocyte subsets and chemotherapy efficacy may reflect the broad impact of standard regimens on immune reconstitution. Limitations include the small sample size, absence of functional experiments, and failure to assess the influence of co-infections. Future studies should expand the cohort and integrate multi-omics data to validate these findings.
ConclusionPatients with HIV-DLBCL have distinctive alterations in peripheral blood lymphocyte subsets, such as a decreased absolute count and percentage of CD4+ T cells, in comparison to individuals with DLBCL. These alterations appear age-related and showed no significant association with prior antiretroviral therapy. The therapeutic effect of chemotherapy for HIV-DLBCL, however, might not be impacted by the low absolute count and percentage of CD4+ T-cells in peripheral blood, as well as whether or not they had previously received antiretroviral therapy.
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