Characterization of Human Immunodeficiency Virus Gag-Specific Gamma Interferon-Expressing Cells following Protective Mucosal Immunization with Alphavirus Replicon Particles

Gupta, Surabhi; Janani, R.; Bin, Qian; Luciw, Paul A.; Greer, Catherine E.; Perri, Sílvia Helena Venturoli; Legg, Harold; Donnelly, John; Barnett, Susan W.; O’Hagan, Derek T.; Polo, John M.; Vajdy, Michael

doi:10.1128/jvi.79.11.7135-7145.2005

Cited by 36 publications

(32 citation statements)

References 62 publications

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“…immunizations with the combined VRP prime-Env protein boost regimen, while only a subset of animals primed by mucosal routes showed any protection, and none of the macaques that received recombinant VRP alone were protected. VRP vaccines similar to those used here were previously shown to elicit both humoral and cellular immune responses when delivered parenterally to small animals and macaques (16,17,38) and protection of macaques as measured by significant reductions in acute-phase virus load following intravenous homologous SHIV SF162 challenge (57). The present work extends the latter result to demonstrate the complete protective efficacy of the recombinant VRP prime plus Env protein boost approach in the face of a relevant mucosal challenge with a closely related virus, SHIV.…”

Section: Discussionsupporting

confidence: 71%

“…Two VEE/SIN VRP preparations were made, one encoding SIV GagPol and another encoding HIV-1 SF162 gp140⌬V2. VRP were generated by cotransfection of in vitro-transcribed RNA species, harvested as culture supernatants, and purified as described previously (16,38). Replicon particle titers were determined by intracellular staining of expressed Env followed by overnight infection of BHK-21 cells with serial dilutions of particles and expressed as infectious units (IU) per ml.…”

Section: Methodsmentioning

confidence: 99%

“…The chimeric (VEE/SIN) alpha-virus vector system used in this study was derived from Venezuelan equine encephalitis virus (VEE) and the Sindbis virus (SIN). The recombinant VEE, SIN, and Semliki viruses expressing SIV or HIV antigens as well as antigens from a diverse and growing list of pathogens have been evaluated extensively in animals by several groups (6,15,16,17,22,32,34,35,36,38,42,44,57,58). The chimeric alphavirus replicon particles (VRP) used here were designed to combine the immune potency of the VEE replicon with the safety profile of the SIN structural proteins (38).…”

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confidence: 99%

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Antibody-Mediated Protection against Mucosal Simian-Human Immunodeficiency Virus Challenge of Macaques Immunized with Alphavirus Replicon Particles and Boosted with Trimeric Envelope Glycoprotein in MF59 Adjuvant

Barnett

Burke

Sun

et al. 2010

J Virol

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After more than 25 years of human immunodeficiency virus (HIV) research, a prophylactic vaccine able to control or prevent the worldwide spread of HIV/AIDS remains an elusive goal. Recent results in Thailand with the recombinant canary pox (ALVAC-HIV, vCP1521; Sanofi-Pasteur) prime-gp120 (AIDSVAX B/E) protein boost vaccine approach give us hope that such a vaccine is achievable (45). Nevertheless, the results from this trial as well as the disappointing outcome of the Step Study trial (7, 29, 46) vividly highlight the need to better understand the immune correlates of protection and the immune responses engendered by the diverse new vaccine technologies currently under evaluation (13,18,20,49). In the case of viral vectors, this is particularly critical, as the spectrum of immune responses elicited in animal models does not necessarily predict those eventually observed in human clinical trials and will require more thorough evaluations in order to identify the most predictive models. At the moment, nonhuman primate models, such as simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infection of macaques appear to be the most informative for guiding vaccine development (3,24,47,55), and more rigorous application of these models has begun to yield new and encouraging insights into protective immunity (5,19,27,56). Moreover, as most HIV transmissions occur through mucosal membranes, understanding the correlates of protection, following successful vaccinations, against mucosal challenge is of strong interest.Alphaviruses are positive-sense single-stranded 11.5-kb RNA viruses in the Togaviridae family. They are relatively simple enveloped viruses of approximately 60-nm diameter that have a cytoplasmic RNA-based life cycle and mature at the plasma membranes of infected cells. Recombinant alphavirus replicon particles used for vaccine applications are composed of a replicon vector that encodes the viral replicases (nonstructural proteins [NSPs]) and the vaccine antigen of interest and two packaging vectors that encode the major viral structural proteins (capsid and glycoproteins E1 and E2) required for particle formation. The chimeric (VEE/SIN) alpha-* Corresponding author. Mailing address: Novartis Vaccines and Diagnostics,

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Section: Discussionsupporting

confidence: 71%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Antibody-Mediated Protection against Mucosal Simian-Human Immunodeficiency Virus Challenge of Macaques Immunized with Alphavirus Replicon Particles and Boosted with Trimeric Envelope Glycoprotein in MF59 Adjuvant

Barnett

Burke

Sun

et al. 2010

J Virol

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“…Mice were challenged with viruses by intravaginal inoculation as described previously (17). Five days before each inoculation, mice were treated subcutaneously with 2 mg of depot medroxyprogesterone acetate (Depo-Provera).…”

Section: Methodsmentioning

confidence: 99%

A Neonatal Fc Receptor-Targeted Mucosal Vaccine Strategy Effectively Induces HIV-1 Antigen-Specific Immunity to Genital Infection

Palaniyandi

Zeng

et al. 2011

J Virol

103

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“…Some of these candidates have not yet been tested in humans but are non-toxic and elicit significant CMI responses in animal models. These include alphaviruses [55][56][57], polioviruses [58], and rhabdoviruses [52]. Candidate vaccine vectors in more advanced stages of development are under evaluation in human clinical trials.…”

Section: Discussionmentioning

confidence: 99%

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

Parker

Rottinghaus

Zajac

et al. 2007

Vaccine

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We have constructed a replication competent, γ 1 34.5-deleted Herpes Simplex Virus type 1 (HSV-1) vector (J200) that expresses the gag gene from Human Immunodeficiency Virus type-1, primary isolate 89.6 (HIV-1 89.6 ), as a candidate vaccine for HIV-1. J200 replicates in vitro, resulting in abundant Gag protein production and accumulation in the extracellular media. Immunization of Balb/ c mice with a single intraperitoneal injection of J200 elicited strong Gag-specific CD8 responses, as measured by intracellular IFN-γ staining and flow cytometry analysis. Responses were highest between 6 weeks and 4 months, but persisted at 9 months post-immunization, the last time-point evaluated. These data highlight the potential utility of neuroattenuated, replication-competent HSV-1 vectors for delivery of HIV-1 immunogens.

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Characterization of Human Immunodeficiency Virus Gag-Specific Gamma Interferon-Expressing Cells following Protective Mucosal Immunization with Alphavirus Replicon Particles

Cited by 36 publications

References 62 publications

Antibody-Mediated Protection against Mucosal Simian-Human Immunodeficiency Virus Challenge of Macaques Immunized with Alphavirus Replicon Particles and Boosted with Trimeric Envelope Glycoprotein in MF59 Adjuvant

Antibody-Mediated Protection against Mucosal Simian-Human Immunodeficiency Virus Challenge of Macaques Immunized with Alphavirus Replicon Particles and Boosted with Trimeric Envelope Glycoprotein in MF59 Adjuvant

A Neonatal Fc Receptor-Targeted Mucosal Vaccine Strategy Effectively Induces HIV-1 Antigen-Specific Immunity to Genital Infection

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

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