Antibodies against full-length Tat protein and some low-molecular-weight Tat-peptides correlate with low or undetectable viral load in HIV-1 seropositive patients

Re, Maria Carla; Vignoli, M.; Furlini, G.; Gibellini, Davide; Colangeli, Vincenzo; Vitone, Francesca; Plaça, M. La

doi:10.1016/s1386-6532(00)00189-x

Cited by 83 publications

(61 citation statements)

References 39 publications

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“…In good agreement with previous studies [19][20][21], at least two antigenic regions recognised by antibodies from HIV-infected individuals were identified in Tat (Table 2; Figs. 1 and 2).…”

Section: Discussionsupporting

confidence: 92%

“…reacting with Tat peptides 6-14, 36-50 and 46-60 are more frequent in SP individuals with undetectable viral load [21]. These discrepancies may be due to the fine specificity of antibody tested and to their titre in the serum of infected patients.…”

Section: Discussionmentioning

confidence: 99%

“…Tat antibodies are detected in the serum of HIV-infected patients and a number of short linear Tat epitopes recognised by IgM or IgG patients' antibodies have been characterised in several regions of the protein [17][18][19][20][21]. Independent groups have shown that, in contrast to antibodies to Env, Nef and Gag, the level of Tat antibodies is elevated in long-term nonor slow-progressors (SP), and is low in fast-progressors (FP), their decline in asymptomatic individuals would be related to the imminence of AIDS [21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

“…Independent groups have shown that, in contrast to antibodies to Env, Nef and Gag, the level of Tat antibodies is elevated in long-term nonor slow-progressors (SP), and is low in fast-progressors (FP), their decline in asymptomatic individuals would be related to the imminence of AIDS [21][22][23][24][25]. It has been reported further that the presence of Tat natural IgM antibodies present in normal individuals (and chimpanzees, but not from other primates and mice) and reacting with functional Tat regions might have some influence on the course of AIDS progression [23,26].…”

Section: Introductionmentioning

confidence: 99%

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Specificity and effect on apoptosis of Tat antibodies from vaccinated and SHIV-infected rhesus macaques and HIV-infected individuals

Belliard

Romieu

Zagury

et al. 2003

Vaccine

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Recent contributions have demonstrated that actively secreted Tat protein plays an important functional role in human immunodeficiency virus-1 (HIV-1) infection and that Tat antibodies might interfere with disease progression by blocking the protein extracellularly. In this context we have studied the recognition of several Tat mutants as well as various synthetic Tat fragments by anti-Tat monoclonal antibodies and by IgG antibodies from a large collection of slow and fast-progressor infected individuals. We have also tested the sera from simian/human immunodeficiency virus (SHIV)-infected macaques with these Tat peptides. Important differences were found between long-term non-progressors and fast-progressors, and between human and monkey sera in terms of antibody specificity. Rabbits and macaques were immunised with several Tat peptides and we found that certain antibody subsets from immunised animals recognised the cognate protein Tat and had the capacity to inhibit Tat-induced apoptosis of T cells. Such antibodies might be important for controlling Tat-induced death in cells uninfected by HIV-1.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Specificity and effect on apoptosis of Tat antibodies from vaccinated and SHIV-infected rhesus macaques and HIV-infected individuals

Belliard

Romieu

Zagury

et al. 2003

Vaccine

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“…Specifically, antibody (Ab) responses to Tat have been associated with non-progression to AIDS [23][24][25][26][27][28]. Similarly, anti-Tat CTLs have been shown to inversely correlate with progression to AIDS [29,30].…”

Section: Introductionmentioning

confidence: 99%

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

Maggiorella

Baroncelli

Michelini

et al. 2004

Vaccine

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Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.

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Efficient mucosal delivery of the HIV‐1 Tat protein using the synthetic lipopeptide MALP‐2 as adjuvant

et al. 2003

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A major requirement for HIV/AIDS research is the development of a mucosal vaccine that stimulates humoral and cell-mediated immune responses at systemic and mucosal levels, thereby blocking virus replication at the entry port. Thus, a vaccine prototype based on biologically active HIV-1 Tat protein as antigen and the synthetic lipopeptide, macrophageactivating lipopeptide-2 (MALP-2), as a mucosal adjuvant was developed. Intranasal administration to mice stimulated systemic and mucosal anti-Tat antibody responses, and Tatspecific T cell responses, that were more efficient than those observed after i.p. immunization with Tat plus incomplete Freund's adjuvant. Major linear B cell epitopes mapped within aa 1-20 and 46-60, whereas T cell epitopes were identified within aa 36-50 and 56-70. These epitopes have also been described in vaccinated primates and in HIV-1-infected individuals with better prognosis. Analysis of the anti-Tat IgG isotypes in serum, and the cytokine profile of spleen cells indicated that a dominant Th1 helper response was stimulated by Tat plus MALP-2, as opposed to the Th2 response observed with Tat plus incomplete Freund's adjuvant. Tat-specific IFN-+ -producing cells were significantly increased only in response to Tat plus MALP-2. These data suggest that Malp-2 may represent an optimal mucosal adjuvant for candidate HIV vaccines based on Tat alone or in combination with other HIV antigens.

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Antibodies against full-length Tat protein and some low-molecular-weight Tat-peptides correlate with low or undetectable viral load in HIV-1 seropositive patients

Cited by 83 publications

References 39 publications

Specificity and effect on apoptosis of Tat antibodies from vaccinated and SHIV-infected rhesus macaques and HIV-infected individuals

Specificity and effect on apoptosis of Tat antibodies from vaccinated and SHIV-infected rhesus macaques and HIV-infected individuals

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

Efficient mucosal delivery of the HIV‐1 Tat protein using the synthetic lipopeptide MALP‐2 as adjuvant

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