Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine

Cafaro, Aurelio; Caputo, Antonella; Fracasso, Claudio; Maggiorella, Maria Teresa; Goletti, Delia; Baroncelli, Silvia; Pace, Monica; Sernicola, Leonardo; Koanga-Mogtomo, Martin Luther; Betti, Monica; Borsetti, Alessândra; Belli, Roberto; Åkerblom, Lennart; Corrias, Franco; Buttò, Stefano; Heeney, Jonathan L.; Verani, P; Titti, Fausto; Ensoli, Barbara

doi:10.1038/9488

Cited by 260 publications

(236 citation statements)

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“…At each time-point bleedings were performed for routine blood chemistry tests and immunological determinations. The vaccination protocols and schedules have been reported elsewhere [34][35][36]. After 14-18 weeks from the last boost, all animals were challenged intravenously (i.v.)…”

Section: Vaccination Protocol and Virus Challengementioning

confidence: 99%

“…The virus stock used was derived from a cynomolgus macaque inoculated with the original SHIV89.6P from rhesus monkeys [42]. Both the original viral stock grown in a rhesus macaque and the one grown in a cynomolgus monkey were highly pathogenic in M. fascicularis [34,35]. The pathogenicity in cynomolgus monkeys of both virus stocks was confirmed by the progression to AIDS and death (within 46 weeks from the inoculum) of four out of six and four out of seven cynomolgus monkeys infected, respectively, with the rhesus-or cynos-derived viral stock [35].…”

Section: Vaccination Protocol and Virus Challengementioning

confidence: 99%

“…The pathogenicity in cynomolgus monkeys of both virus stocks was confirmed by the progression to AIDS and death (within 46 weeks from the inoculum) of four out of six and four out of seven cynomolgus monkeys infected, respectively, with the rhesus-or cynos-derived viral stock [35]. The two naive control animals, monkeys 2 and 12, included as additional control at the time of the challenge, were inoculated with a three-fold higher (28 MID 50 ) or three-fold lower (2.8 MID 50 ) viral inoculum, respectively [34][35][36].…”

Section: Vaccination Protocol and Virus Challengementioning

confidence: 99%

“…Until week 14 post-challenge quantitation of SHIV89.6P RNA copies was performed only in the Bayer-Chiron Diagnostics reference Testing Laboratory (Amsterdam, The Netherlands) by a branched DNA (bDNA) signal amplification assay recognizing the pol region of the SIVmac251 strain, as described [34], with a cut-off of 1,500 RNA copies/ml. Between week 14 and 28 post-challenge quantitation of SHIV89.6P RNA copies was performed by both the bDNA method and by a more sensitive quantitative competitive RNA-polymerase chain reaction (QC-RNA-PCR, cut-off: 50 RNA copies/ml) as already described [43].…”

Section: Quantitation Of the Shiv Rna Copies In Plasmamentioning

confidence: 99%

“…Pre-clinical studies in mice and monkeys have shown that vaccination with a biologically active native HIV-1 Tat protein or with tat DNA is safe [34][35][36][37][38], elicits both humoral and cell-mediated Tat-specific immune responses [34][35][36][37][38], and, in cynomolgus monkeys, controls infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset in the protected animals [34][35][36]. Similar results of protection were reported in the SIV model with viral vectors (Semliki Forest Virus and Modified Vaccinia Ankara Virus) expressing the SIV-Tat and -Rev genes [39].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Vaccination Protocol and Virus Challengementioning

confidence: 99%

Section: Vaccination Protocol and Virus Challengementioning

confidence: 99%

Section: Vaccination Protocol and Virus Challengementioning

confidence: 99%

Section: Quantitation Of the Shiv Rna Copies In Plasmamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Highly stable oligomerization forms of HIV-1 Tat detected by monoclonal antibodies and requirement of monomeric forms for the transactivating function on the HIV-1 LTR

Tosi¹,

Meazza²,

Barbaro³

et al. 2000

Eur. J. Immunol.

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The use of newly generated murine monoclonal antibodies directed against distinct epitopes of a functionally active, chemically synthesized HIV‐1 Tat protein has permitted the identification of several molecular forms including monomers, dimers and trimers. Dimers and trimers are particularly stable and resistant to strong reducing conditions. Through epitope mapping it has been possible to demonstrate that the major immunodominant epitope is contained within the basic region of the Tat protein and is lost after oligomerization of the molecule. In contrast, N‐terminal, C‐terminal and conformation‐dependent epitopes are still accessible to mAb specific recognition after Tat oligomerization. Moreover, by using a quantitative HIV‐LTR transactivation assay depending upon exogenous Tat, we could extrapolate the amount of functional Tat produced by cell lines stably transfected with the viral transactivator. More importantly, we could show that only the monomeric form of exogenous Tat is the relevant functional form acting in cells harbouring the HIV‐1 LTR promoter.

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Identification, molecular cloning and functional characterization of NKp46 and NKp30 natural cytotoxicity receptors inMacaca fascicularis NK cells

et al. 2001

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Natural killer (NK) cell recognition and function in humans is regulated by multiple cell surface receptors. The "on" signal leading to NK cell triggering is primarily mediated by natural cytotoxicity receptors (NCR). Analysis of NK cells in primate animal models is of particular relevance because NK cells may play an essential role in host defenses against infections. We analyzed Macaca fascicularis PBMC and in vitro‐derived NK cell populations and clones by cytofluorometry, using a wide panel of mAb, and by cytolytic activity assays. In addition, RT‐PCR strategyand transient transfections were used to isolate M. fascicularis NCR. NCR‐specific mAb reactivity (anti‐NKp46 and anti‐NKp30) was present on M. fascicularis PBMC and on NK cell cultures. Macaque NCR were functional in both redirected killing and in mAb‐mediated masking assays. Cloning of macNKp46 and macNKp30 NCR homologous genes showed a high sequence similarity (86 % and88 %, respectively) with their human counterparts. Attempts at identifying NKp44 surface reactivity and at cloning the macaque homologue were unsuccessful. NKp46 and NKp30 NCRs, but not NKp44, are highly conserved in M. fascicularis NK cells. This suggests the possibility of a staged appearance of the NCR during phylogenesis and provides a useful tool for the study of natural immunity correlates of protection in primate SIV/SHIV infection models.

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Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine

Cited by 260 publications

References 50 publications

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

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

Highly stable oligomerization forms of HIV-1 Tat detected by monoclonal antibodies and requirement of monomeric forms for the transactivating function on the HIV-1 LTR

Identification, molecular cloning and functional characterization of NKp46 and NKp30 natural cytotoxicity receptors inMacaca fascicularis NK cells

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