Suppression of Acute Viremia by Short-Term Postexposure Prophylaxis of Simian/Human Immunodeficiency Virus SHIV-RT-Infected Monkeys with a Novel Reverse Transcriptase Inhibitor (GW420867) Allows for Development of Potent Antiviral Immune Responses Resulting in Efficient Containment of Infection

Mori, Kazuyasu; Yasutomi, Yasuhiro; Sawada, Shuzo; Villinger, François; Sugama, Kazushige; Rosenwith, Brigitte; Heeney, Jonathan L.; Überla, Klaus; Yamazaki, Shudo; Ansari, Aftab A.; Rübsamen‐Waigmann, Helga

doi:10.1128/jvi.74.13.5747-5753.2000

Cited by 70 publications

(59 citation statements)

References 31 publications

(29 reference statements)

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“…Indeed, virus-specific CD4 ϩ lymphoproliferative responses (LPR) 2 are associated with CD8 ϩ T cell responses in HIV-1 infection (5,19,20). Control of viral rebound following the suspension of antiretroviral therapy in primary HIV-1 or SIV infection of humans or monkeys is associated with both CD4 ϩ and CD8 ϩ T cell responses to HIV or SIV Ags (21)(22)(23)(24). Altogether, these results indicate an important role for cell-mediated immunity in control of HIV/SIV replication and suggest that an important feature of effective HIV vaccine must be its ability to induce high frequency of virus-specific CD4 ϩ and CD8 ϩ T cells.…”

Section: Effective Cytolytic Activity Of Cd8mentioning

confidence: 99%

Potentiation of Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cell Responses by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen

Hel¹,

Tsai²,

Thornton³

et al. 2001

The Journal of Immunology

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T cell-mediated immune responses play an important role in the containment of HIV-1 replication. Therefore, an effective vaccine against HIV-1 should be able to elicit high frequencies of virus-specific CD8+ and CD4+ T cells. The highly attenuated poxvirus-based vaccine candidate, NYVAC-SIV-gag-pol-env (NYVAC-SIV-gpe), has been shown to induce and/or expand SIV-specific CD4+ and CD8+ T cell responses in both naive and infected macaques. In this study, the immunogenicity of NYVAC-SIV-gpe alone was compared with a combination regimen where priming with an optimized DNA-SIV-gag-env vaccine candidate was followed by a NYVAC-SIV-gpe boost. In macaques immunized with the prime-boost regimen, the extent and durability of CD8+ T cell response to an immunodominant SIV gag epitope was increased and these animals recognized a broader array of subdominant SIV epitopes in the cytolytic assay. In addition, the prime-boost regimen significantly enhanced the proliferative responses to both SIV gag and env proteins. Thus, the combination of these vaccine modalities may represent a valuable strategy in the development of a vaccine for HIV.

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Section: Effective Cytolytic Activity Of Cd8mentioning

confidence: 99%

Potentiation of Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cell Responses by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen

Hel¹,

Tsai²,

Thornton³

et al. 2001

The Journal of Immunology

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“…88 Rhesus macaques experimentally infected with SHIV while on ART showed long-lasting virus-specific cell-mediated immune responses despite low and/or undetectable viral loads compared to control animals, leading to long-term disease protection. 89 The generation of immune responses in PrEPinfected animals could lead to synergy with vaccine-induced immune responses. Nonhuman primate studies support the concept of a significant protective effect against repeated low dose intrarectal SIV and SHIV challenge, after rectal application of tenofovir prior to virus challenge.…”

Section: Mucosal Exposure In the Absence Of Chronic Infection Can Indmentioning

confidence: 99%

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

Excler

Rida²,

Priddy

et al. 2011

AIDS Research and Human Retroviruses

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While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2Â2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present.

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“…18 The sensitivity of the plasma viral RNA detection utilizing this technique was determined to be 500 copies/mL plasma.…”

Section: Viral Load Determinationsmentioning

confidence: 99%

“…Clearly, a number of defects ranging from loss of lymphocyte specificities and subsets to signaling defects of CD4 ϩ T cells from HIV-1-infected patients have been documented. [16][17][18][19][20] Yet definitive proof for such defects cannot be obtained from the study of humans infected with HIV-1, since it would involve the use of autologous cells obtained prior For personal use only. on May 10, 2018. by guest www.bloodjournal.org From to infection.…”

Section: Introductionmentioning

confidence: 99%

Adoptive transfer of simian immunodeficiency virus (SIV) naı̈ve autologous CD4+ cells to macaques chronically infected with SIV is sufficient to induce long-term nonprogressor status

Villinger

Brice

Mayne

et al. 2002

Blood

Self Cite

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IntroductionAlthough highly active antiretroviral therapy (HAART) has a major beneficial effect on HIV-1-infected individuals, 1,2 it is clear that the next major therapeutic breakthrough requires a better definition of strategies for full immune reconstitution. 3 One of the challenges in achieving this goal is our lack of understanding of the precise spectrum or kinetics of the development of immune dysfunction in individual HIV-infected patients and strategies best suited to reconstitute such immune defects. Although virus-specific cytotoxic T lymphocytes (CTLs) clearly play a major role in eliminating virus-infected cells, 4-6 development and maintenance of such CTL pools require CD4 ϩ T helper cell function and an appropriate balance of cytokines. 3,7,8 It is also clear that innate immune mechanisms play a major role particularly during the initial stages of infection, 9,10 influencing the viral load set point, and that virus-neutralizing antibodies contribute to the containment of cell-free virus infection of naive cells. 11,12 Thus, a variety of immune reconstitution strategies need to be explored, some of which may be of benefit to those patients who were initiated on HAART during acute infection, whereas others may be more appropriate to patients with chronic infection. Since the primary target of HIV-1 infection is the CD4 ϩ T cells and the depletion of those cells is one of the major consequences of infection, our laboratory has initially focused on seeking methodologies for the replenishment of this cell lineage.Several studies aimed at immune reconstitution have previously been performed utilizing autologous unfractionated and in vitro expanded CD8 ϩ T cells from HIV-1-infected patients. [13][14][15] Transient decreases in viral load and increases in CD4 ϩ T-cell counts have been achieved utilizing such immune reconstitution therapies. However, these studies used autologous cells collected after HIV infection. Thus, lack of a more profound effect could be due to either an abnormal microenvironment for the adoptively transferred cells to home, survive, and/or execute immune function, or an intrinsic defect in the transferred T cells, as a direct and/or indirect effect of the virus infection. Clearly, a number of defects ranging from loss of lymphocyte specificities and subsets to signaling defects of CD4 ϩ T cells from HIV-1-infected patients have been documented. [16][17][18][19][20] Yet definitive proof for such defects cannot be obtained from the study of humans infected with HIV-1, since it would involve the use of autologous cells obtained prior For personal use only. on May 10, 2018. by guest www.bloodjournal.org From to infection. Hence, such mechanistic questions require the use of an animal model, which provides infection-induced immune dysfunction within an immune system comparable to humans. Simian immunodeficiency virus (SIV)-infected nonhuman primates provide such a model, in which we may attempt to distinguish among the above-mentioned 2 possibilities since the CD4 ϩ T cells can be colle...

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Suppression of Acute Viremia by Short-Term Postexposure Prophylaxis of Simian/Human Immunodeficiency Virus SHIV-RT-Infected Monkeys with a Novel Reverse Transcriptase Inhibitor (GW420867) Allows for Development of Potent Antiviral Immune Responses Resulting in Efficient Containment of Infection

Cited by 70 publications

References 31 publications

Potentiation of Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cell Responses by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen

Potentiation of Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cell Responses by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

Adoptive transfer of simian immunodeficiency virus (SIV) naı̈ve autologous CD4+ cells to macaques chronically infected with SIV is sufficient to induce long-term nonprogressor status

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