Related Experiment Video
Updated: Dec 28, 2025
09:26
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
14.4K
Immune checkpoint modulation enhances HIV-1 antibody induction
Todd Bradley1,2,3,4, Masayuki Kuraoka5, Chen-Hao Yeh5
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA. tcbradley@cmh.edu.
Nature Communications
|February 21, 2020
Summary
Targeting immune checkpoints like CTLA-4 or OX40 during HIV vaccination can boost protective antibody responses. This approach enhances germinal center activity, a key factor in generating effective HIV-1 broadly neutralizing antibodies (bnAbs).
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Inducing broadly neutralizing antibodies (bnAbs) against HIV-1 remains a major challenge for vaccine development.
- Many bnAbs originate from rare B cell precursors with unique genetic traits, potentially influenced by host regulatory mechanisms.
Purpose of the Study:
- To investigate if modulating immune checkpoints can enhance HIV-1 broadly neutralizing antibody (bnAb) responses.
- To evaluate the impact of targeting CTLA-4, PD-1, or OX40 in combination with HIV envelope (Env) vaccines.
Main Methods:
- Administered antibodies targeting CTLA-4, PD-1, or OX40 alongside HIV Env vaccines in rhesus macaques and bnAb precursor knock-in mice.
- Analyzed immune responses, including germinal center B cells, T follicular helper cells, and plasma neutralizing antibody titers.
Main Results:
- CTLA-4 blockade enhanced HIV-1 Env antibody responses in macaques.
- In bnAb precursor mice, CTLA-4 blockade or OX40 agonism increased germinal center activity and plasma neutralizing antibodies.
Conclusions:
- Modulating CTLA-4 or OX40 immune checkpoints during HIV vaccination promotes germinal center activity.
- These strategies show promise for enhancing HIV-1 Env antibody responses and advancing vaccine development.
Related Concept Videos
01:29Immune Response Against Viral Pathogens
1.6K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.6K
01:27Cytotoxic T Cells-mediated Immune Response
6.3K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.3K
01:22T Cell Activation and Clonal Selection
14.4K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
14.4K
01:27Tumor Immunotherapy
1.7K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.7K