Human immunodeficiency virus type 1 Rev- and Tat-specific cytotoxic T lymphocyte frequencies inversely correlate with rapid progression to AIDS.

Baalen, Carel A. van; Pontesilli, O.; Huisman, Robin C.; Geretti, Anna María; Klein, Michél R.; Wolf, F de; Miedema, Frank; Gruters, Rob A.; Osterhaus, A. D. M. E.

doi:10.1099/0022-1317-78-8-1913

Cited by 182 publications

(110 citation statements)

References 35 publications

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“…It contains regulatory proteins Tat and about 69% of the CTL epitope-rich Cterminus of Nef, which are expressed abundantly and early after HIV infection. In tissue culture, CTL recognizing early proteins killed HIV-infected cells before they produced more virus virions, 22,23 and produced chemokines that inhibit HIV replication. [24][25][26][27] In vivo, vaccineinduced CTL against early proteins provided a degree of protection against pathogenic virus challenges.…”

Section: Design Of the Renta Immunogenmentioning

confidence: 99%

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

Nkolola

et al. 2004

Gene Ther

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For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell vaccine consisting of HIV-1 clade A Gag-derived immunogen HIVA delivered in a prime-boost regimen by a DNA plasmid and modified vaccinia virus Ankara (MVA). Here, we describe engineering and preclinical development of a second immunogen RENTA, which will be used in combination with the present vaccine in a four-component DNA/HIVA-RENTA prime-MVA/HIVA-RENTA boost formulation. RENTA is a fusion protein derived from consensus HIV clade A sequences of Tat, reverse transcriptase, Nef and gp41. We inactivated the natural biological activities of the HIV components and confirmed immunogenicities of the pTHr.RENTA and MVA.RENTA vaccines in mice. Furthermore, we demonstrated in mice and rhesus monkeys broadening of HIVAelicited T-cell responses by a parallel induction of HIVA-and RENTA-specific responses recognizing multiple HIV epitopes.

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Section: Design Of the Renta Immunogenmentioning

confidence: 99%

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

Nkolola

et al. 2004

Gene Ther

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“…Early inhibition of Tat function should contribute to control of viral replication and slowing of AIDS progression. In fact, Tat-specific CTLs are associated with control of virus replication early in infection [18] and both anti-Tat antibody and Tatspecific CTLs have been correlated with reduced viremia and slow progression to AIDS [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection

Florese

Wiseman

Venzon

et al. 2008

Vaccine

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Protection afforded by HIV Tat-based vaccines has differed in Indian rhesus and Mauritian cynomolgus macaques. We evaluated native Tat and Ad-HIVtat priming/Tat-boosting regimens in both species. Both vaccines were immunogenic. Only the Ad-tat regimen modestly reduced acute viremia in rhesus macaques after SHIV 89.6P challenge. Confounding variables uncovered in Mauritian macaques included significant associations of susceptibility to infection with MHC class IB and class II H2 and H5 haplotypes, and resistance to infection with class IB haplotypes H3 and H6. Although protection here was limited, Tat-based vaccines incorporating other HIV components have shown greater efficacy. Combination strategies should be further explored.

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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]. Of importance, Tat is conserved in its immunogenic regions among all M subtypes, and Tat B clade is recognized to the same extent by sera from South African, Ugandan and Italian individuals infected with A, B, C and D virus clades [28].…”

Section: Introductionmentioning

confidence: 99%

“…Of importance, Tat is conserved in its immunogenic regions among all M subtypes, and Tat B clade is recognized to the same extent by sera from South African, Ugandan and Italian individuals infected with A, B, C and D virus clades [28]. Further, studies in humans [29,30] and in monkeys indicate that anti-Tat CTLs are key to control virus replication early after primary infection, and that they exert a selective immune pressure on the virus leading to the appearance of slowly replicating and apparently less pathogenic escape mutants [31].…”

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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Human immunodeficiency virus type 1 Rev- and Tat-specific cytotoxic T lymphocyte frequencies inversely correlate with rapid progression to AIDS.

Cited by 182 publications

References 35 publications

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection

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

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