Publications by authors named "Ndongala M Lubaki"
Article Synopsis
- Some monoclonal antibodies (mAbs) from filovirus infection survivors can potentially protect against new infections, but the role of natural infection-induced antibodies in causing antibody-dependent enhancement (ADE) is still unclear.
- A study found that all mAbs tested facilitated ADE at low concentrations, regardless of their specific properties, indicating that ADE is a widespread phenomenon in these antibodies.
- Modifying certain parts of an mAb to change its interaction with receptors led to partial protection in live models, implying that ADE might hinder the effectiveness of antibody protection and could help spread filovirus infections.
Article Synopsis
- - A study reveals that Ebola virus glycoprotein (GP) helps the virus to weaken the host's immune system, leading to higher infection rates and cell death in immune cells.
- - The harmful effects of GP were reduced when the Toll-like receptor 4 pathway was blocked, suggesting a potential therapeutic target.
- - High levels of GP were also found in the fluid from cells treated with Ebola vaccines, indicating that shed GP may contribute to both Ebola disease progression and negative reactions linked to the vaccines.
Article Synopsis
- Ebola Virus Disease (EVD) is driven by an exaggerated immune response called a "cytokine storm," which is influenced by the activation of T lymphocytes.
- The protein T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) plays a crucial role in EBOV infection, with studies showing that Tim-1 mice have better survival rates despite minimal differences in viral load.
- EBOV binds to T lymphocytes via Tim-1 and induces a significant inflammatory response, leading to changes in cytokine production and activation of T helper cells, which contributes to the severity of the cytokine storm associated with fatal disease outcomes.
Article Synopsis
- Ebola virus (EBOV) infections lead to fatal outcomes often preceded by a syndrome similar to sepsis and a significant drop in T cell counts (lymphopenia), which correlates with mortality rates.
- The study found that the EBOV glycoprotein (GP) contributes to T cell death by binding to CD4+ T cells via TLR4, leading to cell death mechanisms such as apoptosis and necrosis.
- Additionally, EBOV exposure causes increased differentiation of monocytes, enhancing their susceptibility to infection, which further exacerbates T cell death and impairs the immune response.
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line.
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- Ebola virus infections lead to poor immune responses, specifically involving T-lymphocytes, which are crucial for fighting infections.
- Research showed that modifying EBOV proteins (VP24 and VP35) can enhance the immune response, particularly by increasing the activation and function of dendritic cells and T-cells.
- These modifications also improve B-cell activity and increase the activation of natural killer (NK) cells, contributing to a more effective immune response against the virus.
Direct delivery of aerosolized vaccines to the respiratory mucosa elicits both systemic and mucosal responses. This vaccine strategy has not been tested for Ebola virus (EBOV) or other hemorrhagic fever viruses. Here, we examined the immunogenicity and protective efficacy of an aerosolized human parainfluenza virus type 3-vectored vaccine that expresses the glycoprotein (GP) of EBOV (HPIV3/EboGP) delivered to the respiratory tract.
View Article and Find Full Text PDFUnlabelled: Ebola virus (EBOV) causes a severe hemorrhagic fever with a deficient immune response, lymphopenia, and lymphocyte apoptosis. Dendritic cells (DC), which trigger the adaptive response, do not mature despite EBOV infection. We recently demonstrated that DC maturation is unblocked by disabling the innate response antagonizing domains (IRADs) in EBOV VP35 and VP24 by the mutations R312A and K142A, respectively.
View Article and Find Full Text PDFEbola virus (EBOV) infections are characterized by deficient T lymphocyte responses, T lymphocyte apoptosis, and lymphopenia in the absence of direct infection of T lymphocytes. In contrast, dendritic cells (DC) are infected but fail to mature appropriately, thereby impairing the T cell response. We investigated the contributions of EBOV proteins in modulating DC maturation by generating recombinant viruses expressing enhanced green fluorescent protein and carrying mutations affecting several potentially immunomodulating domains.
View Article and Find Full Text PDFThis paper reports on an assessment of community preparedness for HIV vaccine trials in the Democratic Republic of Congo. Formative research was conducted in the capital city of Kinshasa during the period October 2003 to March 2004 to answer questions pertinent to planning trials of a preventive HIV vaccine and to identify related issues. Twenty-seven in-depth interviews and two focus groups were held with potential trial participants and community leaders.
View Article and Find Full Text PDFAs the HIV-1 pandemic becomes increasingly complex, the genetic characterization of HIV strains bears important implications for vaccine research. To better understand the molecular evolution of HIV-1 viral diversity, we performed a comparative molecular analysis of HIV strains collected from high-risk persons in Kinshasa, Democratic Republic of Congo (DRC). Analysis of the gag-p24, env-C2V3 and -gp41 regions from 83 specimens collected in 1999-2000 revealed that 44 (53%) had concordant subtypes in the three regions (14 subsubtype A1, 10 subtype G, 8 subtype D, 5 subtype C, 2 each subsubtype F1 and CRF01_AE, and one each of subtypes H and J, and subsubtype A2, while the remaining 39 (47%) had mosaic genomes comprising multiple subtype combinations.
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