Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P)

Cafaro, Aurelio; Titti, Fausto; Fracasso, Claudio; Maggiorella, Maria Teresa; Baroncelli, Silvia; Caputo, Antonella; Goletti, Delia; Borsetti, Alessândra; Pace, Monica; Fanales-Belasio, Emanuele; Ridolfi, Barbara; Negri, Donatella; Sernicola, Leonardo; Belli, Roberto; Corrias, Franco; Macchia, Iole; Leone, Pasqualina; Michelini, Zuleika; Haaft, Peter ten; Buttò, Stefano; Verani, P; Ensoli, Barbara

doi:10.1016/s0264-410x(01)00002-0

Cited by 138 publications

(118 citation statements)

References 57 publications

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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 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%

“…SHIV proviral copy number was determined by a semi-quantitative DNA PCR utilizing 1 g of DNA and amplifying a 496 bp region of the gag gene of SIVmac239, as already described [34,36]. The lower limit of detection was 1 SHIV proviral copy/ g of DNA.…”

Section: Proviral Dna Detectionmentioning

confidence: 99%

“…Virus isolation and cytoviremia were performed by co-culturing CD8-depleted PBMCs with CEMx174 cells in the presence of phytohemoagglutinin (PHA, 2 g/ml) and recombinant human interleukin-2 (rhIL-2) (50 IU/ml), as already described [34][35][36].…”

Section: Virus Isolation and Cell Associated Viral Load (Cytoviremia)mentioning

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: Proviral Dna Detectionmentioning

confidence: 99%

Section: Virus Isolation and Cell Associated Viral Load (Cytoviremia)mentioning

confidence: 99%

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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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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Adjuvants and Subunit Vaccines

Giudice¹,

Rappuoli²

2010

Topley &Amp; Wilson's Microbiology and Microbial Infections

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Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P)

Cited by 138 publications

References 57 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

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

Adjuvants and Subunit Vaccines

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