scholarly journals Development and Evaluation of an Ebola Virus Glycoprotein Mucin-Like Domain Replacement System as a New DC-Targeting Vaccine Approach Against HIV-1

2021 ◽  
Author(s):  
Zhujun Ao ◽  
Lijun Wang ◽  
Hiva Azizi ◽  
Titus Olukitibi Abiola ◽  
Gary Kobinger ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Fusion Protein ◽  
Hiv Infection ◽  
Ebola Virus ◽  
Mouse Serum ◽  
Virus Like Particles ◽  
Hiv Antibodies ◽  
Vaccine Approach ◽  
Anti Hiv ◽  
Hiv 1

The development of efficient vaccine approaches against HIV infection remains challenging in the vaccine field. We herein developed an Ebola virus envelope glycoprotein (EboGP)-based chimeric fusion protein system and demonstrated that replacement of the mucin-like domain (MLD) of EboGP with HIV C2-V3-C3 (134 aa) or C2-V3-C3-V4-C4-V5-C5 (243 aa) polypeptides (EbGPΔM-V3 and EbGPΔM-V3-V5, respectively) still maintained the efficiency of EboGP-mediated viral entry into human macrophages and dendritic cells (DCs). Animal studies using mice revealed that immunization with virus-like particles (VLPs) containing the above chimeric proteins, especially EbGPΔM-V3, induced significantly more potent anti-HIV antibodies than HIV gp120 alone in mouse serum and vaginal fluid. Moreover, the splenocytes isolated from mice that immunized with VLPs containing EbGPΔM-V3 produced significantly higher levels of IFN-γ, IL-2, IL-4, IL-5 and MIP-1α. Additionally, we demonstrated that co-expression of EbGPΔM-V3 and the HIV Env glycoprotein in a recombinant vesicular stomatitis virus (rVSV) vector elicited robust anti-HIV antibodies that may have specifically recognized outside or inside the C2-V3-C3 region of HIV-1 gp120 and cross-reacted with the gp120 from different HIV strains. Thus, this study has demonstrated the great potential of this DC-targeting vaccine platform as a new vaccine approach for improving immunogen delivery and increasing vaccine efficacy. Importance Currently, there are more than 38.5 million reported cases of HIV globally. To date, there is no approved vaccine for HIV-1 infection. Thus, the development of an effective vaccine against HIV infection remains a global priority. This study revealed the efficacy of a novel Dendritic Cells (DC)-targeted vaccination approach against HIV-1. The results have clearly shown that the immunization of mice with virus-like particles (VLPs) and VSVs containing HIV Env and a fusion protein comprised of a DC-targeting domain of Ebola GP with HIV C2-V3-C3 polypeptides (EbGPΔM-V3) could induce robust immune responses against HIV-1 Env and/or Gag in sera and vaginal mucosa. These findings have provided a proof of concept of this novel and efficient DC-targeting vaccine approach in delivering various antigenic polypeptides of HIV-1 and/or other emergent infections to the host antigen-presenting cells to prevent HIV and other viral infections.

scholarly journals HIV-1 Tat Promotes Integrin-Mediated HIV Transmission to Dendritic Cells by Binding Env Spikes and Competes Neutralization by Anti-HIV Antibodies

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e48781 ◽  
Author(s):  
Paolo Monini ◽  
Aurelio Cafaro ◽  
Indresh K. Srivastava ◽  
Sonia Moretti ◽  
Victoria A. Sharma ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hiv Transmission ◽  
Hiv Antibodies ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals The Differential Anti-HIV Effect of a New Humic Substance-Derived Preparation in Diverse Cells of the Immune System

Acta Naturae ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 68-76
Author(s):  
G. V. Kornilaeva ◽  
A. E. Siniavin ◽  
A. Schultz ◽  
A. Germann ◽  
C. Moog ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Humic Substance ◽  
Immune Cells ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Infection Inhibition ◽  
Toxic Concentrations ◽  
Anti Hiv ◽  
Hiv 1

The anti-HIV activity of a new humic substance-derived preparation has been studied in individual pools of immune cells (CD4+ T lymphocytes, macrophages, dendritic cells). Near-complete inhibition of the HIV infection (by more than 90%) was achieved by treating each of the abovementioned cell types with non-toxic concentrations of the preparation. The inhibitory effect demonstrates the possibility of preventing the depletion of a significant portion of functionally important immune cells. A comparative study of infection inhibition in individual cell pools has allowed us to reveal the differences in the preparations effectiveness in each of the cell populations. A R5-tropic HIV-1 infection in macrophages exhibited maximum sensitivity to the preparation: 90% and 50% inhibition of the infection were observed in the presence of concentrations as low as 1.4 and 0.35 g/ml, respectively. A 15- and 19-fold higher concentration was required to achieve the same extent of inhibition in dendritic cells infected with the same strain. The effectiveness of the drug in CD4 + T lymphocytes is quite comparable to its effectiveness in macrophages. The drug is universally effective for both the T- and M-tropic variants of HIV-1.

scholarly journals Early Detection of Human Immunodeficiency Virus Type 1-Specific B-Lymphocyte-Derived Antibodies in a High-Risk Population

2009 ◽  
Vol 16 (7) ◽  
pp. 1060-1065 ◽  
Author(s):  
Odd Odinsen ◽  
David Parker ◽  
Frans Radebe ◽  
Mikey Guness ◽  
David A Lewis
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
B Cell ◽  
Immunodeficiency Virus ◽  
Hiv Antibodies ◽  
P24 Antigen ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT Diagnosis of acute human immunodeficiency virus (HIV) infection, a key driver of the HIV epidemic, remains a public health challenge. The PlasmAcute technology offers an opportunity to detect early anti-HIV antibody responses. B lymphocytes (B cells) were isolated from the blood of seronegative miners in South Africa by using the PlasmAcute method. B-cell lysates and paired sera were tested for anti-HIV-1 antibodies by two different enzyme-linked immunosorbent assays; immunoreactivity was confirmed by Western blotting. All volunteers were tested for HIV type 1 (HIV-1) viral load, p24 antigen, and CD4 count. Sera from HIV-seronegative men who had positive viral loads and were positive for p24 antigen were retested for anti-HIV antibodies after immune complex dissociation. Anti-HIV antibodies were detected in lysates from 16/259 subjects without immunoreactivity in paired sera. Four subjects, one of whom had a positive viral load initially, subsequently seroconverted. Six subjects showed transient anti-HIV-1 antibodies in the lysates and tested negative for all markers at the follow-up. Five subjects without follow-up data initially had lysate-positive/serum-negative samples, and these cases were classified as inconclusive. One subject had lysate antibodies and a detectable viral load but was seronegative at follow-up. In conclusion, lysate-derived anti-HIV-1 B-cell antibodies can be detected prior to seroconversion and earlier than or contemporary with HIV-1 RNA detection.

scholarly journals Dendritic Cells/Macrophages-Targeting Feature of Ebola Glycoprotein and its Potential as Immunological Facilitator for Antiviral Vaccine Approach

2019 ◽  
Vol 7 (10) ◽  
pp. 402
Author(s):  
Titus Abiola Olukitibi ◽  
Zhujun Ao ◽  
Mona Mahmoudi ◽  
Gary A. Kobinger ◽  
Xiaojian Yao
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Immunological Approach ◽  
Vaccine Approach ◽  
Acquired Immune Responses ◽  
Diverse Virus

In the prevention of epidemic and pandemic viral infection, the use of the antiviral vaccine has been the most successful biotechnological and biomedical approach. In recent times, vaccine development studies have focused on recruiting and targeting immunogens to dendritic cells (DCs) and macrophages to induce innate and adaptive immune responses. Interestingly, Ebola virus (EBOV) glycoprotein (GP) has a strong binding affinity with DCs and macrophages. Shreds of evidence have also shown that the interaction between EBOV GP with DCs and macrophages leads to massive recruitment of DCs and macrophages capable of regulating innate and adaptive immune responses. Therefore, studies for the development of vaccine can utilize the affinity between EBOV GP and DCs/macrophages as a novel immunological approach to induce both innate and acquired immune responses. In this review, we will discuss the unique features of EBOV GP to target the DC, and its potential to elicit strong immune responses while targeting DCs/macrophages. This review hopes to suggest and stimulate thoughts of developing a stronger and effective DC-targeting vaccine for diverse virus infection using EBOV GP.

scholarly journals DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells

2004 ◽  
Vol 200 (10) ◽  
pp. 1279-1288 ◽  
Author(s):  
Jean-François Arrighi ◽  
Marjorie Pion ◽  
Eduardo Garcia ◽  
Jean-Michel Escola ◽  
Yvette van Kooyk ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Synapse Formation ◽  
Model Systems ◽  
Hiv 1 ◽  
Infectious Synapse

Dendritic cells (DCs) are essential for the early events of human immunodeficiency virus (HIV) infection. Model systems of HIV sexual transmission have shown that DCs expressing the DC-specific C-type lectin DC-SIGN capture and internalize HIV at mucosal surfaces and efficiently transfer HIV to CD4+ T cells in lymph nodes, where viral replication occurs. Upon DC–T cell clustering, internalized HIV accumulates on the DC side at the contact zone (infectious synapse), between DCs and T cells, whereas HIV receptors and coreceptors are enriched on the T cell side. Viral concentration at the infectious synapse may explain, at least in part, why DC transmission of HIV to T cells is so efficient. Here, we have investigated the role of DC-SIGN on primary DCs in X4 HIV-1 capture and transmission using small interfering RNA–expressing lentiviral vectors to specifically knockdown DC-SIGN. We demonstrate that DC-SIGN− DCs internalize X4 HIV-1 as well as DC-SIGN+ DCs, although binding of virions is reduced. Strikingly, DC-SIGN knockdown in DCs selectively impairs infectious synapse formation between DCs and resting CD4+ T cells, but does not prevent the formation of DC–T cells conjugates. Our results demonstrate that DC-SIGN is required downstream from viral capture for the formation of the infectious synapse between DCs and T cells. These findings provide a novel explanation for the role of DC-SIGN in the transfer and enhancement of HIV infection from DCs to T cells, a crucial step for HIV transmission and pathogenesis.

scholarly journals Prevalence of and risk factors for HIV infection in blood donors and various population subgroups in Ethiopia

2002 ◽  
Vol 128 (2) ◽  
pp. 221-228 ◽  
Author(s):  
R. E. J. H. SENTJENS ◽  
Y. SISAY ◽  
H. VRIELINK ◽  
D. KEBEDE ◽  
H. J. ADÈR ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hiv Infection ◽  
Sexual Behaviour ◽  
Blood Donors ◽  
Transmitted Disease ◽  
Urban Residents ◽  
Sexual Transmitted Disease ◽  
Low Prevalence ◽  
Anti Hiv ◽  
Hiv 1

The aim was to determine the prevalence of HIV infection and risk factors for HIV infection in various population subgroups in Ethiopia. Serum panels from blood donors (n = 2610), from various population subgroups in Ethiopia were tested for anti-HIV-1/2 by ELISA. All ELISA repeatedly reactive samples were subjected for confirmation by immunoblot (IB) and anti-HIV-1 and anti-HIV-2 specific ELISAs. 155/2610 (5·9%) blood donors were HIV-1 infected. Of pregnant women, 84/797 (10·5%) were HIV-1 infected, and 1/797 (0·1%) was HIV-2 infected. 1/240 (0·4%) individuals from the rural population were HIV-1 infected. 198/480 (41·3%) female attendees, and 106/419 (25·3%) male attendees at sexual transmitted disease (STD) clinics were HIV-1 infected. One (0·2%) male, and 2 (0·4%) female STD patients were infected with both HIV-1 and HIV-2. It was concluded that the prevalence of HIV-1 infection varied from 0·4% among urban residents to 25·3–41·3% among STD attendees. There is a low prevalence of HIV-2 present in Ethiopian subjects. Risky sexual behaviour is significantly associated with HIV-infection in Ethiopia.

scholarly journals Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells

2015 ◽  
Vol 11 (7) ◽  
pp. e1005024 ◽  
Author(s):  
Mariana G. Bego ◽  
Édouard Côté ◽  
Nick Aschman ◽  
Johanne Mercier ◽  
Winfried Weissenhorn ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cross Talk ◽  
Plasmacytoid Dendritic Cells ◽  
The Cross ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Enhanced Neutralization of HIV by Antibodies Displayed on the S-Layer of Caulobacter crescentus

2011 ◽  
Vol 55 (12) ◽  
pp. 5547-5552 ◽  
Author(s):  
Mark Duval ◽  
Christopher J. Lewis ◽  
John F. Nomellini ◽  
Marc S. Horwitz ◽  
John Smit ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Caulobacter Crescentus ◽  
Low Cost ◽  
Content Type ◽  
Innovative Methods ◽  
Hiv Antibodies ◽  
The Cost ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACTInnovative methods of prevention are needed to stop the more than two million new HIV-1 infections annually, particularly in women. Local application of anti-HIV antibodies has been shown to be effective at preventing infection in nonhuman primates; however, the concentrations needed are cost prohibitive. Display of antibodies on a particulate platform will likely prolong effectiveness of these anti-HIV agents and lower the cost of goods. Here, we demonstrate that the bacteriumCaulobacter crescentusand its highly expressed surface-layer (S-layer) protein can provide this antibody display platform. Caulobacters displaying protein G, alone or with CD4 codisplay, successfully captured HIV-1-specific antibodies and demonstrated functional neutralization. Compared to soluble antibodies, a neutralizing anti-HIV antibody displayed onCaulobacterwas as effective or more effective at neutralizing diverse HIV-1 isolates. Moreover, when an antibody reactive with an epitope induced by CD4 binding (CD4i) was codisplayed with CD4, there was significant enhancement in HIV-1 neutralization. These results suggest that caulobacters displaying anti-HIV antibodies offer a distinct improvement in the use of antibodies as microbicides. Furthermore, these reagents can specifically evaluate anti-HIV antibodies in concert with other HIV-1 blocking agents to assess the most suitable tools for conversion to scFvs, allowing for direct display within the S-layer protein and further reducing cost of goods. In summary,C. crescentus, which can be easily produced and chemically stabilized at low cost, is well suited for engineering as an effective platform, offering an inexpensive way to produce and deliver HIV-1-specific microbicides.

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