The Importance of Cellular Immune Response to HIV: Implications for Antibody Production and Vaccine Design

Brenna, Elena; McMichael, Andrew J.

doi:10.1089/dna.2021.0520

Cited by 4 publications

(3 citation statements)

References 44 publications

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“…A critical fact underlying the HIV pandemic is that T cells serve as a double-edged sword: acting as targets for HIV infection and replication, while also mediating anti-viral functions required to fight the virus (64,65). The findings presented here suggest that previous explanations for the observed increased risk of HIV infection in the context of BV may have focused too heavily on the target cell side of that sword without appreciating BV's impact on altering T cell functionality.…”

Section: Discussionmentioning

confidence: 81%

Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility

MacLean,

Tsegaye,

Graham

et al. 2024

Preprint

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Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent in reproductive-age women worldwide. Adverse outcomes associated with BV include an increased risk of sexually acquired Human Immunodeficiency Virus (HIV), yet the immunological mechanisms underlying this association are not well understood. To investigate BV driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and peripheral blood mononuclear cells (PBMC). Immunofluorescence analysis of genital mucosal tissues revealed a reduced density of CD3+CD4+CCR5+cells in the VT lamina propria of individuals with compared to those without BV (median 243.8 cells/mm2BV-vs 106.9 cells/mm2BV+, p=0.043). High-parameter flow cytometry of VT biopsies revealed an increased frequency in individuals with compared to those without BV of dysfunctional CD39+conventional CD4+T cells (Tconv) (median frequency 15% BV-vs 30% BV+, padj=0.0331) and tissue-resident CD69+CD103+Tconv (median frequency 24% BV-vs 38% BV+, padj=0.0061), previously reported to be implicated in HIV acquisition and replication. Our data suggests that BV elicits diverse and complex VT T cell alterations and expands on potential immunological mechanisms that may promote adverse outcomes including HIV susceptibility.

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Section: Discussionmentioning

confidence: 81%

Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility

MacLean,

Tsegaye,

Graham

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…During the infectious response, CD8 + T cells are necessary for the direct destruction of infected cells, while CD4 + T cells promote the induction of CD8 + T cells and support the maturation of highly specific antibodies produced from B-lymphocytes ( 108 , 109 ). B-cells undergo iterative cycles of proliferation, immunoglobulin mutation, and antigen selection for the generation of highly specific antibodies in specialized immune cells in the secondary lymphoid organs (germinal centers or GCs) ( 70 , 108 ). After an antigen challenge, GCs activate the B-cells by antigen-specific B-cell surface receptors (BCRs) ( 110 ).…”

Section: Antibody Based Therapies and Vaccinesmentioning

confidence: 99%

“…After an antigen challenge, GCs activate the B-cells by antigen-specific B-cell surface receptors (BCRs) ( 110 ). Each GC generally focuses on one specific antigen and can produce a limited amount of antigen-specific B cells ( 108 ). This process contrasts with the early B-cell responses to antigens in the extrafollicular spaces that result in short-lived antibody-producing cells (plasmablasts) secreting non-mutated antibodies ( 70 , 111 ).…”

Section: Antibody Based Therapies and Vaccinesmentioning

confidence: 99%

Strategies for HIV-1 suppression through key genes and cell therapy

Sorokina,

Anchakova,

Dashinimaev

2023

Front. Med.

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Human immunodeficiency virus type 1 (HIV-1) remains a significant challenge for global public health as limited therapeutic options are available for HIV-infected individuals receiving combination antiretroviral therapy. Additionally, individuals with HIV-1/acquired immunodeficiency syndrome (AIDS) complications have a reduced life expectancy. In recent decades, gene and cell-based strategies have shown promise in achieving a functional cure for HIV-1 infection. The outcomes of therapies with patients in Berlin and London have led to moderate optimism for a highly effective HIV-1 treatment. This review categorizes current strategies for HIV-1 treatment into RNA- and antibody-based therapies, cell and genome editing approaches, and methods for eradicating latent reservoirs. These findings demonstrate how the use of various anti-HIV-1 agents enhances our understanding of HIV-1 infection and may provide important insights for potential HIV-1 treatment.

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Humoral immune response to inactivated COVID-19 vaccination at the 3rd month among people living with HIV

Zou

Ming

et al. 2023

BMC Infect Dis

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Background Research on the immune response to inactivated COVID-19 vaccination among people living with HIV (PLWH) is limited, especially among those with low CD4+ T lymphocyte (CD4 cell) count. This prospective cohort study aimed to assess the humoral immune response to inactivated COVID-19 vaccination among PLWH compared to HIV negative controls (HNCs) and to determine the impact of CD4 cell count on vaccine response among PLWH. Methods The neutralizing antibodies (nAbs) and the specific IgM and IgG-binding antibody responses to the inactivated COVID-19 vaccine at the third month after the second dose of inactivated COVID-19 vaccination were measured among 138 PLWH and 35 HNCs. Multivariable logistic regression and multiple linear regression models were conducted to identify factors associated with the seroconversion rate of antibodies and the magnitude of anti-SARS-CoV-2 antibody titers, respectively. Results At the end of the third month after two doses of vaccination, the seroconversion rates of IgG were comparable between PLWH (44.9%; 95% CI 36.5–53.3%) and HNCs (60.0%; 95% CI 42.9–77.1%), respectively. The median titers and seroconversion rate of nAbs among PLWH were 0.57 (IQR: 0.30–1.11) log10 BAU/mL and 29.0% (95% CI 21.3–36.8%), respectively, both lower than those in HNCs (P < 0.05). After adjusting for age, sex, comorbidities, and CD4 cell count, the titers and seroconversion rate of nAbs were comparable between PLWH and HNCs (P > 0.05). Multivariable regression analyses showed that CD4 cell count < 200/μL was independently associated with lower titers and seroconversion rate of nAbs among PLWH (P < 0.05). A positive correlation was observed between the CD4 cell count and nAbs titers in PLWH (Spearman's ρ = 0.25, P = 0.0034). Conclusion Our study concluded that the immune response to inactivated COVID-19 vaccination among PLWH was independently associated with CD4 cell count, PLWH with lower CD4 cell count showed a weaker humoral immune response, especially those with CD4 cell count < 200/μL. This finding suggests that expanding COVID-19 vaccination coverage among PLWH is impendency. In addition, aggressive ART should be carried out for PLWH, especially for those with low CD4 cell count, to improve the immune response to vaccines.

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The Importance of Cellular Immune Response to HIV: Implications for Antibody Production and Vaccine Design

Cited by 4 publications

References 44 publications

Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility

Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility

Strategies for HIV-1 suppression through key genes and cell therapy

Humoral immune response to inactivated COVID-19 vaccination at the 3rd month among people living with HIV

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