Design and In Vivo Immunogenicity of a Polyvalent Vaccine Based on SIVmac Regulatory Genes

Hel, Zdeněk; Tryniszewska, Elżbieta; Tsai, Wen-Po; Johnson, Julie; Harrod, Robert; Fullen, Jake; Kalyanaraman, V. S.; Altman, John D.; McNally, Jonathan P.; Karpova, Tatiana S.; Felber, Barbara K.; Tartaglia, Jim; Franchini, Genoveffa

doi:10.1089/104454902760330156

Cited by 10 publications

(6 citation statements)

References 56 publications

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“…Therefore, vaccines aimed at eliciting a large number of polyclonal CTLs against these antigens may prove effective at blocking virus expression during the early phases of the acute infection, minimizing the selection of escape variants. Along this line, a novel vaccine approach based on a polyvalent chimeric protein in which the genes coding for HIV-1 Tat, Rev and Nef has been recently developed and found safe and immunogenic in macaques [66].…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…All animals received mixes of DNA vectors producing secreted and intracellular forms of gag and env. In addition, as indicated in Table 1, most animals received vectors expressing intracellular forms of a fusion protein polNTV consisting of Pol, Nef, Tat, and Vif proteins or alternatively a vector expressing a fusion (RTNV) of Rev-Tat-Nef (ReTaNef [7,8]) and Vif proteins. Several point mutations were introduced into pol to inactivate protease (D25A, T26A, and G27A), reverse transcriptase (D186A and D187A), RNaseH (E478A), and integrase (D64A, D116A, and E152A).…”

Section: Animalsmentioning

confidence: 99%

Long-Lasting Decrease in Viremia in Macaques Chronically Infected with Simian Immunodeficiency Virus SIVmac251 after Therapeutic DNA Immunization

Gegerfelt¹,

Rosati²,

Alicea

et al. 2007

J Virol

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Rhesus macaques chronically infected with highly pathogenic simian immunodeficiency virus (SIV) SIVmac251 were treated with antiretroviral drugs and vaccinated with combinations of DNA vectors expressing SIV antigens. Vaccination during therapy increased cellular immune responses. After the animals were released from therapy, the virus levels of 12 immunized animals were significantly lower (P ‫؍‬ 0.001) compared to those of 11 animals treated with only antiretroviral drugs. Vaccinated animals showed a persistent increase in immune responses, thus indicating both a virological and an immunological benefit following DNA therapeutic vaccination. Several animals show a long-lasting decrease in viremia, suggesting that therapeutic vaccination may provide an additional benefit to antiretroviral therapy.

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“…However, the breadth of neutralization was still limited to the strains that were included in the vaccine formulation and vaccination did not afford protection from a heterologous SHIV challenge. A different type of polyvalent vaccine based on macaque simian immunodeficiency virus (SIVmac) regulatory genes, rev , tat , and nef , was demonstrated to be immunogenic in SIVmac-251-infected macaques as evidenced by an expansion of virus-specific CD8+ T cell virus responses but no protection was studied in this report [94]. Given the setback of the STEP trial, polyvalent vaccines with a focus on eliciting broad protective antibody responses are clearly indicated.…”

Section: Argument For the Use Of The Polyvalent Strategy For Hiv-1 Vamentioning

confidence: 99%

Polyvalent AIDS Vaccines

Serrano²,

Wang³

2010

CHR

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A major hurdle in the development of a global HIV-1 vaccine is viral diversity. For close to three decades, HIV vaccine development has focused on either the induction of T cell immune responses or antibody responses, and only rarely on both components. After the failure of the STEP trial, the scientific community concluded that a T cell-based vaccine would likely not be protective if the T cell immune responses were elicited against only a few dominant epitopes. Similarly, for vaccines focusing on antibody responses, one of the main criticisms after VaxGen’s failed Phase III trials was on the limited antigen breadth included in the two formulations used. The successes of polyvalent vaccine approaches against other antigenically variable pathogens encourage implementation of the same approach for the design of HIV-1 vaccines. A review of the existing HIV-1 vaccination approaches based on the polyvalent principle is included here to provide a historical perspective for the current effort of developing a polyvalent HIV-1 vaccine. Results summarized in this review provide a clear indication that the polyvalent approach is a viable one for the future development of an effective HIV vaccine.

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Design and In Vivo Immunogenicity of a Polyvalent Vaccine Based on SIVmac Regulatory Genes

Cited by 10 publications

References 56 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

Long-Lasting Decrease in Viremia in Macaques Chronically Infected with Simian Immunodeficiency Virus SIVmac251 after Therapeutic DNA Immunization

Polyvalent AIDS Vaccines

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