HIV-1 Tat-specific IgG antibodies in high-responders target a B-cell epitope in the cysteine-rich domain and block extracellular Tat efficiently

Kashi, Venkatesh P.; Jacob, Rajesh; Paul, Siddhartha; Nayak, Kaustuv; Satish, Bhuthiah; Swaminathan, Soumya; Satish, K.S.; Ranga, Udaykumar

doi:10.1016/j.vaccine.2009.08.078

Cited by 10 publications

(14 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the course of the study, 86% of patients developed antiTat IgG above detection levels; however, the mean percentage of patients with measurable anti-Tat IgG at each time point was 56%, which is in agreement with previous findings [17,19]. This variability of the anti-Tat IgG present in the sera may explain why different studies have reported different prevalence's of anti-Tat IgG [16][17][18][19][20][21][22][23][24]. It is possible that if the study were continued, all patients may develop an antiTat IgG response.…”

Section: Discussionsupporting

confidence: 88%

“…However, specific anti-Tat IgG are detected in the sera of 10-95% of HIV infected patients depending upon the method used [16][17][18][19][20][21][22][23][24]. In some studies, the presence of these antibodies has been correlated with slow or nonprogression of HIV disease [17,22,23,25]; however, in other studies no such correlation has been observed [24].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antiretroviral Therapy Does Not Block the Secretion of the Human Immunodeficiency Virus Tat Protein

Mediouni¹,

Darque²,

Baillat³

et al. 2012

IDDT

View full text Add to dashboard Cite

Tat is a viral protein secreted from HIV infected cells and extra cellular Tat is suspected to prevent destruction of HIV infected cells from cells of the cellular immunity. The effect of anti retroviral therapy (ART) on Tat secretion has never been investigated. In this study, we tested for antibody reactivity against Tat variants representative of the main HIV subtypes in HIV positive patients receiving ART with undetectable viral loads ( < 40 copies/mL) over the course of one year with a blood sampling every three months. For each of theses five blood sampling, an average of 50 % of patients had Anti-Tat IgG, it turned out that 86% of patients could recognize Tat at least in one blood sampling during the course of the study. Amazingly, anti-Tat IgG appeared and/or disappeared in 66 % of patients. Only 20% had anti-Tat IgG remaining persistently while 14% were consistently without anti Tat IgG in the five blood sampling. No significant correlation was found between anti-Tat IgG and CD4+ T cell, CD8+ T cell and B cell counts revealing the incapacity of these anti Tat IgG to neutralize extra cellular Tat. Interestingly the absence and then the appearance of anti-Tat IgG in patients suggest the presence of HIV infected cells in the blood that may constitute a significant reservoir of HIV infected cells. As a conclusion antiretroviral therapy does not block the secretion of Tat and may explain why HIV infected cells can survive in spite of an effective ART treatment.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Antiretroviral Therapy Does Not Block the Secretion of the Human Immunodeficiency Virus Tat Protein

Mediouni¹,

Darque²,

Baillat³

et al. 2012

IDDT

View full text Add to dashboard Cite

show abstract

“…5A). Both anti-Tat MAbs were then tested in an HLM1 cell-based viral rescue assay (31)(32)(33). The NT Tat-specific MAb NT3 2D1.1 almost completely neutralized Tat transactivation at 40 g/ml.…”

Section: Resultsmentioning

confidence: 99%

“…In this provirus (HXB2), the initiation codon of tat had been mutated to a termination codon. The assay consists of supplying exogenous Tat protein and monitoring viral replication by measuring the viral core antigen (p24) released into cell supernatants, as described previously (31). Briefly, HLM1 cells were seeded into 96-well plates (20,000 cells/well in 200 l of minimal essential medium [MEM]; Sigma-Aldrich), supplemented with 5% equine serum (Life Technologies).…”

Section: Animalsmentioning

confidence: 99%

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

Bachler

Humbert

Palikuqi

et al. 2013

J Virol

View full text Add to dashboard Cite

cIdentifying immune correlates of protection is important to develop vaccines against infectious diseases. We designed a novel, universally applicable strategy to profile the antibody (Ab) repertoire of protected vaccine recipients, using recombinant phages encoding random peptide libraries. The new approach, termed "protection-linked (PL) biopanning," probes the Ab paratopes of protected vaccinees versus those with vaccine failure. As proof of concept, we screened plasma samples from vaccinated rhesus macaques (RMs) that had completely resisted multiple mucosal challenges with R5-tropic simian-human immunodeficiency viruses (SHIVs). The animals had been immunized with a multicomponent vaccine (multimeric HIV-1 gp160, HIV-1 Tat, and SIV Gag-Pol particles). After PL biopanning, we analyzed the phagotopes selected for amino acid homologies; in addition to the expected Env mimotopes, one recurring motif reflected the neutralizing Ab epitope at the N terminus (NT) of HIV-1 Tat. Subsequent binding and functional assays indicated that anti-Tat NT Abs were present only in completely or partially protected RMs; peak viremia of the latter was inversely correlated with anti-Tat NT Ab titers. In contrast, highly viremic, unvaccinated controls did not develop detectable Abs against the same epitope. Based upon the protective effect observed in vivo, we suggest that Tat should be included in multicomponent HIV-1 vaccines. Our data highlight the power of the new PL-biopanning strategy to identify Ab responses with significant association to vaccine protection, regardless of the mechanism(s) or targets of the protective Abs. PL biopanning is also unbiased with regard to pathogens or disease model, making it a universal tool.T he design of a safe, effective vaccine is desirable to control the AIDS pandemic. In order to improve future vaccine candidates, it is important to understand the protective mechanism(s) leading to reduced virus acquisition (1). Thus, correlates of infection risk for the recent RV144 vaccine efficacy trial (2) are the subject of intense study (3,4). However, additional information can be gained by dissecting immune responses in biologically relevant animal models where immunization induced complete protection from immunodeficiency virus challenge(s) (5, 6).Recent results of active (7,8) and passive (9) immunization trials in humans and in nonhuman primates suggested that antihuman immunodeficiency virus type 1 (HIV-1) Env antibodies (Abs) can have protective roles even in the absence of virus neutralization, implying that other Ab-mediated mechanisms may be involved in preventing mucosal virus acquisition. Thus, the ability to profile Ab epitopes associated with protection might help to identify potential targets for future HIV-1 vaccines.Random peptide phage display has been used to dissect Ab responses in the context of primate immunodeficiency virus infections, and several studies have identified HIV-1 or simian-human immunodeficiency virus (SHIV)-specific peptides (10-14). We developed a novel epitope...

show abstract

“…The results demonstrated increased protection in macaques vaccinated with the multiple antigen vaccine after challenge with SHIV (Mooij et al, 2004). However, tat is a poor immunogen and only induces antibody responses in a few HIV-infected individuals (Kashi et al, 2009) and thus it was not surprising that the inclusion of additional antigens increased protection in this instance. Furthermore, when the immune responses were compared, higher frequencies of tat-specific IFN-␥, IL-2 and IL-4 producing T cells were detected in macaques vaccinated with tat only compared with macaques vaccinated with tat, env and gag (Mooij et al, 2004).…”

Section: Discussionmentioning

confidence: 92%

Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag

Garrod

Gargett

et al. 2014

Virus Research

View full text Add to dashboard Cite

HIV-1 Tat-specific IgG antibodies in high-responders target a B-cell epitope in the cysteine-rich domain and block extracellular Tat efficiently

Cited by 10 publications

References 47 publications

Antiretroviral Therapy Does Not Block the Secretion of the Human Immunodeficiency Virus Tat Protein

Antiretroviral Therapy Does Not Block the Secretion of the Human Immunodeficiency Virus Tat Protein

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag

Contact Info

Product

Resources

About