The Experts below are selected from a list of 64275 Experts worldwide ranked by ideXlab platform

Scott G. Hansen - One of the best experts on this subject based on the ideXlab platform.

  • profound early conTrol of highly paThogenic siv by an effecTor Memory T Cell vaccine
    Nature, 2011
    Co-Authors: Scott G. Hansen, Nathan Whizin, Kelli Oswald, Lia Coynejohnson, Julia C Ford, Matthew S Lewis, Abigail B Ventura, Colette M Hughes, Rebecca Shoemaker, Tonya Swanson
    Abstract:

    The acquired immunodeficiency syndrome (AIDS)-causing lenTiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effecTively evade hosT immuniTy and, once esTablished, infecTions wiTh These viruses are only rarely conTrolled by immunological mechanisms. However, The iniTial esTablishmenT of infecTion in The firsT few days afTer mucosal exposure, before viral disseminaTion and massive replicaTion, may be more vulnerable To immune conTrol. Here we reporT ThaT SIV vaccines ThaT include rhesus cyTomegalovirus (RhCMV) vecTors esTablish indefiniTely persisTenT, high-frequency, SIV-specific effecTor Memory T-Cell (T(EM)) responses aT poTenTial siTes of SIV replicaTion in rhesus macaques and sTringenTly conTrol highly paThogenic SIV(MAC239) infecTion early afTer mucosal challenge. ThirTeen of TwenTy-four rhesus macaques receiving eiTher RhCMV vecTors alone or RhCMV vecTors followed by adenovirus 5 (Ad5) vecTors (versus 0 of 9 DNA/Ad5-vaccinaTed rhesus macaques) manifesTed early compleTe conTrol of SIV (undeTecTable plasma virus), and in Twelve of These ThirTeen animals we observed long-Term (≥1 year) proTecTion. This was characTerized by: occasional blips of plasma viraemia ThaT ulTimaTely waned; predominanTly undeTecTable Cell-associaTed viral load in blood and lymph node mononuclear Cells; no depleTion of effecTor-siTe CD4(+) Memory T Cells; no inducTion or boosTing of SIV Env-specific anTibodies; and inducTion and Then loss of T-Cell responses To an SIV proTein (Vif) noT included in The RhCMV vecTors. ProTecTion correlaTed wiTh The magniTude of The peak SIV-specific CD8(+) T-Cell responses in The vaccine phase, and occurred wiThouT anamnesTic T-Cell responses. Remarkably, long-Term RhCMV vecTor-associaTed SIV conTrol was insensiTive To eiTher CD8(+) or CD4(+) lymphocyTe depleTion and, aT necropsy, Cell-associaTed SIV was only occasionally measurable aT The limiT of deTecTion wiTh ulTrasensiTive assays, observaTions ThaT indicaTe The possibiliTy of evenTual viral clearance. Thus, persisTenT vecTors such as CMV and Their associaTed T(EM) responses mighT significanTly conTribuTe To an efficacious HIV/AIDS vaccine.

  • effecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Lia Coynejohnson, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Issue:Vaccines ThaT induce T Cell responses To simian immunodeficiency virus are able To reduce virus load in infecTed macaques. Such vaccines Typically induce cenTral Memory T Cells ThaT musT expand before gaining full anTiviral funcTions. Picker and his colleagues show ThaT a new replicaTing anTi-SIV vaccine, based on The persisTenTly infecTing cyTomegalovirus, which preferenTially induces effecTor Memory T Cells in mucosal Tissues, can reduce The likelihood ThaT The macaques become infecTed in The firsT place ( pages 244–246 ). The rapid onseT of massive, sysTemic viral replicaTion during primary HIV or simian immunodeficiency virus (SIV) infecTion and The immune evasion capabiliTies of These viruses pose fundamenTal problems for vaccines ThaT depend upon iniTial viral replicaTion To sTimulaTe effecTor T Cell expansion and differenTiaTion1,2,3,4,5. We hypoThesized ThaT vaccines designed To mainTain differenTiaTed effecTor Memory T Cell (TEM Cell) responses5,6 aT viral enTry siTes mighT improve efficacy by impairing viral replicaTion aT iTs earliesT sTage2, and we have Therefore developed SIV proTein-encoding vecTors based on rhesus cyTomegalovirus (RhCMV), The proToTypical inducer of life-long TEM Cell responses7,8,9. RhCMV vecTors expressing SIV Gag, Rev-TaT-Nef and Env persisTenTly infecTed rhesus macaques, regardless of preexisTing RhCMV immuniTy, and primed and mainTained robusT, SIV-specific CD4+ and CD8+ TEM Cell responses (characTerized by coordinaTe Tumor necrosis facTor, inTerferon-γ and macrophage inflammaTory proTein-1β expression, cyToToxic degranulaTion and accumulaTion aT exTralymphoid siTes) in The absence of neuTralizing anTibodies. Compared To conTrol rhesus macaques, These vaccinaTed rhesus macaques showed increased resisTance To acquisiTion of progressive SIVmac239 infecTion upon repeaTed limiTing-dose inTrarecTal challenge, including four macaques who conTrolled recTal mucosal infecTion wiThouT progressive sysTemic disseminaTion. These daTa suggesT a new paradigm for AIDS vaccine developmenT—vaccines capable of generaTing and mainTaining HIV-specific TEM Cells mighT decrease The incidence of HIV acquisiTion afTer sexual exposure.

  • EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Lia Coyne-johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Addendum: EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge

Alfred W. Legasse - One of the best experts on this subject based on the ideXlab platform.

  • effecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Lia Coynejohnson, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Issue:Vaccines ThaT induce T Cell responses To simian immunodeficiency virus are able To reduce virus load in infecTed macaques. Such vaccines Typically induce cenTral Memory T Cells ThaT musT expand before gaining full anTiviral funcTions. Picker and his colleagues show ThaT a new replicaTing anTi-SIV vaccine, based on The persisTenTly infecTing cyTomegalovirus, which preferenTially induces effecTor Memory T Cells in mucosal Tissues, can reduce The likelihood ThaT The macaques become infecTed in The firsT place ( pages 244–246 ). The rapid onseT of massive, sysTemic viral replicaTion during primary HIV or simian immunodeficiency virus (SIV) infecTion and The immune evasion capabiliTies of These viruses pose fundamenTal problems for vaccines ThaT depend upon iniTial viral replicaTion To sTimulaTe effecTor T Cell expansion and differenTiaTion1,2,3,4,5. We hypoThesized ThaT vaccines designed To mainTain differenTiaTed effecTor Memory T Cell (TEM Cell) responses5,6 aT viral enTry siTes mighT improve efficacy by impairing viral replicaTion aT iTs earliesT sTage2, and we have Therefore developed SIV proTein-encoding vecTors based on rhesus cyTomegalovirus (RhCMV), The proToTypical inducer of life-long TEM Cell responses7,8,9. RhCMV vecTors expressing SIV Gag, Rev-TaT-Nef and Env persisTenTly infecTed rhesus macaques, regardless of preexisTing RhCMV immuniTy, and primed and mainTained robusT, SIV-specific CD4+ and CD8+ TEM Cell responses (characTerized by coordinaTe Tumor necrosis facTor, inTerferon-γ and macrophage inflammaTory proTein-1β expression, cyToToxic degranulaTion and accumulaTion aT exTralymphoid siTes) in The absence of neuTralizing anTibodies. Compared To conTrol rhesus macaques, These vaccinaTed rhesus macaques showed increased resisTance To acquisiTion of progressive SIVmac239 infecTion upon repeaTed limiTing-dose inTrarecTal challenge, including four macaques who conTrolled recTal mucosal infecTion wiThouT progressive sysTemic disseminaTion. These daTa suggesT a new paradigm for AIDS vaccine developmenT—vaccines capable of generaTing and mainTaining HIV-specific TEM Cells mighT decrease The incidence of HIV acquisiTion afTer sexual exposure.

  • EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Lia Coyne-johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Addendum: EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge

  • progressive cd4 cenTral Memory T Cell decline resulTs in cd4 effecTor Memory insufficiency and overT disease in chronic siv infecTion
    Journal of Experimental Medicine, 2007
    Co-Authors: Afam A Okoye, Martin Meierschellersheim, Jason M Brenchley, Shoko I Hagen, Joshua M Walker, Mukta Rohankhedkar, Richard Lum, John B Edgar, Shannon L Planer, Alfred W. Legasse
    Abstract:

    Primary simian immunodeficiency virus (SIV) infecTions of rhesus macaques resulT in The dramaTic depleTion of CD4+ CCR5+ effecTor–Memory T (TEM) Cells from exTra-lymphoid effecTor siTes, buT in mosT infecTions, an increased raTe of CD4+ Memory T Cell proliferaTion appears To prevenT collapse of effecTor siTe CD4+ TEM Cell populaTions and acuTe-phase AIDS. EvenTually, persisTenT SIV replicaTion resulTs in chronic-phase AIDS, buT The responsible mechanisms remain conTroversial. Here, we demonsTraTe ThaT in The chronic phase of progressive SIV infecTion, effecTor siTe CD4+ TEM Cell populaTions manifesT a slow, conTinuous decline, and ThaT The degree of This depleTion remains a highly significanT correlaTe of laTe-onseT AIDS. We furTher show ThaT due To persisTenT immune acTivaTion, effecTor siTe CD4+ TEM Cells are predominanTly shorT-lived, and ThaT Their homeosTasis is sTrikingly dependenT on The producTion of new CD4+ TEM Cells from cenTral–Memory T (TCM) Cell precursors. The insTabiliTy of effecTor siTe CD4+ TEM Cell populaTions over Time was noT explained by increasing desTrucTion of These Cells, buT raTher was aTTribuTable To progressive reducTion in Their producTion, secondary To decreasing numbers of CCR5− CD4+ TCM Cells. These daTa suggesT ThaT alThough CD4+ TEM Cell depleTion is a proximaTe mechanism of immunodeficiency, The Tempo of This depleTion and The Timing of disease onseT are largely deTermined by desTrucTion, failing producTion, and gradual decline of CD4+ TCM Cells.

Kelli Oswald - One of the best experts on this subject based on the ideXlab platform.

  • profound early conTrol of highly paThogenic siv by an effecTor Memory T Cell vaccine
    Nature, 2011
    Co-Authors: Scott G. Hansen, Nathan Whizin, Kelli Oswald, Lia Coynejohnson, Julia C Ford, Matthew S Lewis, Abigail B Ventura, Colette M Hughes, Rebecca Shoemaker, Tonya Swanson
    Abstract:

    The acquired immunodeficiency syndrome (AIDS)-causing lenTiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effecTively evade hosT immuniTy and, once esTablished, infecTions wiTh These viruses are only rarely conTrolled by immunological mechanisms. However, The iniTial esTablishmenT of infecTion in The firsT few days afTer mucosal exposure, before viral disseminaTion and massive replicaTion, may be more vulnerable To immune conTrol. Here we reporT ThaT SIV vaccines ThaT include rhesus cyTomegalovirus (RhCMV) vecTors esTablish indefiniTely persisTenT, high-frequency, SIV-specific effecTor Memory T-Cell (T(EM)) responses aT poTenTial siTes of SIV replicaTion in rhesus macaques and sTringenTly conTrol highly paThogenic SIV(MAC239) infecTion early afTer mucosal challenge. ThirTeen of TwenTy-four rhesus macaques receiving eiTher RhCMV vecTors alone or RhCMV vecTors followed by adenovirus 5 (Ad5) vecTors (versus 0 of 9 DNA/Ad5-vaccinaTed rhesus macaques) manifesTed early compleTe conTrol of SIV (undeTecTable plasma virus), and in Twelve of These ThirTeen animals we observed long-Term (≥1 year) proTecTion. This was characTerized by: occasional blips of plasma viraemia ThaT ulTimaTely waned; predominanTly undeTecTable Cell-associaTed viral load in blood and lymph node mononuclear Cells; no depleTion of effecTor-siTe CD4(+) Memory T Cells; no inducTion or boosTing of SIV Env-specific anTibodies; and inducTion and Then loss of T-Cell responses To an SIV proTein (Vif) noT included in The RhCMV vecTors. ProTecTion correlaTed wiTh The magniTude of The peak SIV-specific CD8(+) T-Cell responses in The vaccine phase, and occurred wiThouT anamnesTic T-Cell responses. Remarkably, long-Term RhCMV vecTor-associaTed SIV conTrol was insensiTive To eiTher CD8(+) or CD4(+) lymphocyTe depleTion and, aT necropsy, Cell-associaTed SIV was only occasionally measurable aT The limiT of deTecTion wiTh ulTrasensiTive assays, observaTions ThaT indicaTe The possibiliTy of evenTual viral clearance. Thus, persisTenT vecTors such as CMV and Their associaTed T(EM) responses mighT significanTly conTribuTe To an efficacious HIV/AIDS vaccine.

  • effecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Lia Coynejohnson, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Issue:Vaccines ThaT induce T Cell responses To simian immunodeficiency virus are able To reduce virus load in infecTed macaques. Such vaccines Typically induce cenTral Memory T Cells ThaT musT expand before gaining full anTiviral funcTions. Picker and his colleagues show ThaT a new replicaTing anTi-SIV vaccine, based on The persisTenTly infecTing cyTomegalovirus, which preferenTially induces effecTor Memory T Cells in mucosal Tissues, can reduce The likelihood ThaT The macaques become infecTed in The firsT place ( pages 244–246 ). The rapid onseT of massive, sysTemic viral replicaTion during primary HIV or simian immunodeficiency virus (SIV) infecTion and The immune evasion capabiliTies of These viruses pose fundamenTal problems for vaccines ThaT depend upon iniTial viral replicaTion To sTimulaTe effecTor T Cell expansion and differenTiaTion1,2,3,4,5. We hypoThesized ThaT vaccines designed To mainTain differenTiaTed effecTor Memory T Cell (TEM Cell) responses5,6 aT viral enTry siTes mighT improve efficacy by impairing viral replicaTion aT iTs earliesT sTage2, and we have Therefore developed SIV proTein-encoding vecTors based on rhesus cyTomegalovirus (RhCMV), The proToTypical inducer of life-long TEM Cell responses7,8,9. RhCMV vecTors expressing SIV Gag, Rev-TaT-Nef and Env persisTenTly infecTed rhesus macaques, regardless of preexisTing RhCMV immuniTy, and primed and mainTained robusT, SIV-specific CD4+ and CD8+ TEM Cell responses (characTerized by coordinaTe Tumor necrosis facTor, inTerferon-γ and macrophage inflammaTory proTein-1β expression, cyToToxic degranulaTion and accumulaTion aT exTralymphoid siTes) in The absence of neuTralizing anTibodies. Compared To conTrol rhesus macaques, These vaccinaTed rhesus macaques showed increased resisTance To acquisiTion of progressive SIVmac239 infecTion upon repeaTed limiTing-dose inTrarecTal challenge, including four macaques who conTrolled recTal mucosal infecTion wiThouT progressive sysTemic disseminaTion. These daTa suggesT a new paradigm for AIDS vaccine developmenT—vaccines capable of generaTing and mainTaining HIV-specific TEM Cells mighT decrease The incidence of HIV acquisiTion afTer sexual exposure.

  • EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Lia Coyne-johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Addendum: EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge

Nathan Whizin - One of the best experts on this subject based on the ideXlab platform.

  • profound early conTrol of highly paThogenic siv by an effecTor Memory T Cell vaccine
    Nature, 2011
    Co-Authors: Scott G. Hansen, Nathan Whizin, Kelli Oswald, Lia Coynejohnson, Julia C Ford, Matthew S Lewis, Abigail B Ventura, Colette M Hughes, Rebecca Shoemaker, Tonya Swanson
    Abstract:

    The acquired immunodeficiency syndrome (AIDS)-causing lenTiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effecTively evade hosT immuniTy and, once esTablished, infecTions wiTh These viruses are only rarely conTrolled by immunological mechanisms. However, The iniTial esTablishmenT of infecTion in The firsT few days afTer mucosal exposure, before viral disseminaTion and massive replicaTion, may be more vulnerable To immune conTrol. Here we reporT ThaT SIV vaccines ThaT include rhesus cyTomegalovirus (RhCMV) vecTors esTablish indefiniTely persisTenT, high-frequency, SIV-specific effecTor Memory T-Cell (T(EM)) responses aT poTenTial siTes of SIV replicaTion in rhesus macaques and sTringenTly conTrol highly paThogenic SIV(MAC239) infecTion early afTer mucosal challenge. ThirTeen of TwenTy-four rhesus macaques receiving eiTher RhCMV vecTors alone or RhCMV vecTors followed by adenovirus 5 (Ad5) vecTors (versus 0 of 9 DNA/Ad5-vaccinaTed rhesus macaques) manifesTed early compleTe conTrol of SIV (undeTecTable plasma virus), and in Twelve of These ThirTeen animals we observed long-Term (≥1 year) proTecTion. This was characTerized by: occasional blips of plasma viraemia ThaT ulTimaTely waned; predominanTly undeTecTable Cell-associaTed viral load in blood and lymph node mononuclear Cells; no depleTion of effecTor-siTe CD4(+) Memory T Cells; no inducTion or boosTing of SIV Env-specific anTibodies; and inducTion and Then loss of T-Cell responses To an SIV proTein (Vif) noT included in The RhCMV vecTors. ProTecTion correlaTed wiTh The magniTude of The peak SIV-specific CD8(+) T-Cell responses in The vaccine phase, and occurred wiThouT anamnesTic T-Cell responses. Remarkably, long-Term RhCMV vecTor-associaTed SIV conTrol was insensiTive To eiTher CD8(+) or CD4(+) lymphocyTe depleTion and, aT necropsy, Cell-associaTed SIV was only occasionally measurable aT The limiT of deTecTion wiTh ulTrasensiTive assays, observaTions ThaT indicaTe The possibiliTy of evenTual viral clearance. Thus, persisTenT vecTors such as CMV and Their associaTed T(EM) responses mighT significanTly conTribuTe To an efficacious HIV/AIDS vaccine.

  • effecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Lia Coynejohnson, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Issue:Vaccines ThaT induce T Cell responses To simian immunodeficiency virus are able To reduce virus load in infecTed macaques. Such vaccines Typically induce cenTral Memory T Cells ThaT musT expand before gaining full anTiviral funcTions. Picker and his colleagues show ThaT a new replicaTing anTi-SIV vaccine, based on The persisTenTly infecTing cyTomegalovirus, which preferenTially induces effecTor Memory T Cells in mucosal Tissues, can reduce The likelihood ThaT The macaques become infecTed in The firsT place ( pages 244–246 ). The rapid onseT of massive, sysTemic viral replicaTion during primary HIV or simian immunodeficiency virus (SIV) infecTion and The immune evasion capabiliTies of These viruses pose fundamenTal problems for vaccines ThaT depend upon iniTial viral replicaTion To sTimulaTe effecTor T Cell expansion and differenTiaTion1,2,3,4,5. We hypoThesized ThaT vaccines designed To mainTain differenTiaTed effecTor Memory T Cell (TEM Cell) responses5,6 aT viral enTry siTes mighT improve efficacy by impairing viral replicaTion aT iTs earliesT sTage2, and we have Therefore developed SIV proTein-encoding vecTors based on rhesus cyTomegalovirus (RhCMV), The proToTypical inducer of life-long TEM Cell responses7,8,9. RhCMV vecTors expressing SIV Gag, Rev-TaT-Nef and Env persisTenTly infecTed rhesus macaques, regardless of preexisTing RhCMV immuniTy, and primed and mainTained robusT, SIV-specific CD4+ and CD8+ TEM Cell responses (characTerized by coordinaTe Tumor necrosis facTor, inTerferon-γ and macrophage inflammaTory proTein-1β expression, cyToToxic degranulaTion and accumulaTion aT exTralymphoid siTes) in The absence of neuTralizing anTibodies. Compared To conTrol rhesus macaques, These vaccinaTed rhesus macaques showed increased resisTance To acquisiTion of progressive SIVmac239 infecTion upon repeaTed limiTing-dose inTrarecTal challenge, including four macaques who conTrolled recTal mucosal infecTion wiThouT progressive sysTemic disseminaTion. These daTa suggesT a new paradigm for AIDS vaccine developmenT—vaccines capable of generaTing and mainTaining HIV-specific TEM Cells mighT decrease The incidence of HIV acquisiTion afTer sexual exposure.

  • EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Lia Coyne-johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Addendum: EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge

Charles M. Trubey - One of the best experts on this subject based on the ideXlab platform.

  • effecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Lia Coynejohnson, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Issue:Vaccines ThaT induce T Cell responses To simian immunodeficiency virus are able To reduce virus load in infecTed macaques. Such vaccines Typically induce cenTral Memory T Cells ThaT musT expand before gaining full anTiviral funcTions. Picker and his colleagues show ThaT a new replicaTing anTi-SIV vaccine, based on The persisTenTly infecTing cyTomegalovirus, which preferenTially induces effecTor Memory T Cells in mucosal Tissues, can reduce The likelihood ThaT The macaques become infecTed in The firsT place ( pages 244–246 ). The rapid onseT of massive, sysTemic viral replicaTion during primary HIV or simian immunodeficiency virus (SIV) infecTion and The immune evasion capabiliTies of These viruses pose fundamenTal problems for vaccines ThaT depend upon iniTial viral replicaTion To sTimulaTe effecTor T Cell expansion and differenTiaTion1,2,3,4,5. We hypoThesized ThaT vaccines designed To mainTain differenTiaTed effecTor Memory T Cell (TEM Cell) responses5,6 aT viral enTry siTes mighT improve efficacy by impairing viral replicaTion aT iTs earliesT sTage2, and we have Therefore developed SIV proTein-encoding vecTors based on rhesus cyTomegalovirus (RhCMV), The proToTypical inducer of life-long TEM Cell responses7,8,9. RhCMV vecTors expressing SIV Gag, Rev-TaT-Nef and Env persisTenTly infecTed rhesus macaques, regardless of preexisTing RhCMV immuniTy, and primed and mainTained robusT, SIV-specific CD4+ and CD8+ TEM Cell responses (characTerized by coordinaTe Tumor necrosis facTor, inTerferon-γ and macrophage inflammaTory proTein-1β expression, cyToToxic degranulaTion and accumulaTion aT exTralymphoid siTes) in The absence of neuTralizing anTibodies. Compared To conTrol rhesus macaques, These vaccinaTed rhesus macaques showed increased resisTance To acquisiTion of progressive SIVmac239 infecTion upon repeaTed limiTing-dose inTrarecTal challenge, including four macaques who conTrolled recTal mucosal infecTion wiThouT progressive sysTemic disseminaTion. These daTa suggesT a new paradigm for AIDS vaccine developmenT—vaccines capable of generaTing and mainTaining HIV-specific TEM Cells mighT decrease The incidence of HIV acquisiTion afTer sexual exposure.

  • EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge
    Nature Medicine, 2009
    Co-Authors: Scott G. Hansen, Nathan Whizin, Lia Coyne-johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Kelli Oswald, Cassandra Vieville, Michael K Axthelm, Charles M. Trubey
    Abstract:

    Addendum: EffecTor Memory T Cell responses are associaTed wiTh proTecTion of rhesus monkeys from mucosal simian immunodeficiency virus challenge