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Porichis, Filippos

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Porichis

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Filippos

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Porichis, Filippos
Author's Publications: search.filters.isAuthorOfPublication.8505ac45-1e6c-4986-9f10-2f5abaf24924

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    Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial
    (JAIDS Journal of Acquired Immune Deficiency Syndromes, 2015) Gandhi, Rajesh; Kwon, Douglas; Macklin, Eric; Shopis, Janet R.; McLean, Anna P.; McBrine, Nicole; Flynn, Theresa; Peter, Lauren; Sbrolla, Amy; Kaufmann, Daniel E.; Porichis, Filippos; Walker, Bruce; Bhardwaj, Nina; Barouch, Dan; Kavanagh, Daniel G.
    Background: HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy. Methods: Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10. All participants also received DCs pulsed with keyhole limpet hemocyanin (KLH) to assess whether responses to a neo-antigen could be induced. Results: After immunization, there were no differences in interferon-gamma enzyme-linked immunospot responses to HIV-1 Gag or Nef in the vaccine or placebo group. CD4 proliferative responses to KLH increased 2.4-fold (P = 0.026) and CD8 proliferative responses to KLH increased 2.5-fold (P = 0.053) after vaccination. There were increases in CD4 proliferative responses to HIV-1 Gag (2.5-fold vs. baseline, 3.4-fold vs. placebo, P = 0.054) and HIV-1 Nef (2.3-fold vs. baseline, 6.3-fold vs. placebo, P = 0.009) among vaccine recipients, but these responses were short-lived. Conclusion: Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferon-gamma enzyme-linked immunospot responses. There were increases in proliferative responses to HIV-1 antigens and to a neo-antigen, KLH, but the effects were transient. Dendritic cell vaccination should be optimized to elicit stronger and long-lasting immune responses for this strategy to be effective as an HIV-1 therapeutic vaccine.
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    Increased frequencies of CD8+CD57+ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers
    (International AIDS Society, 2016) Palmer, Christine D; Romero-Tejeda, Marisol; Scully, Eileen P; Lockhart, Ainsley; Seaman, Michael; Goldenthal, Ariel; Piechocka-Trocha, Alicja; Walker, Bruce; Chibnik, Lori; Jost, Stephanie; Porichis, Filippos
    Introduction: An effective prophylactic vaccine against HIV will need to elicit antibody responses capable of recognizing and neutralizing rapidly evolving antigenic regions. The immunologic milieu associated with development of neutralizing antibody breadth remains to be fully defined. In this study, we sought to identify immunological signatures associated with neutralization breadth in HIV controllers. We applied an immune monitoring approach to analyze markers of T cell and myeloid cell activation by flow cytometry, comparing broad neutralizers with low- and non-neutralizers using multivariate and univariate analyses. Methods: Antibody neutralization breadth was determined, and cryopreserved peripheral blood mononuclear cells were stained for T cell and myeloid cell activation markers. Subjects were grouped according to neutralization breadth, and T cell and myeloid cell activation was analyzed by partial least squares discriminant analysis to determine immune signatures associated with high neutralization breadth. Results: We show that neutralization breadth in HIV viraemic controllers (VC) was strongly associated with increased frequencies of CD8+CD57+ T cells and that this association was independent of viral load, CD4 count and time since HIV diagnosis. Conclusions: Our data show elevated frequencies of CD8+CD57+ T cells in VC who develop neutralization breadth against HIV. This immune signature could serve as a potential biomarker of neutralization breadth and should be further investigated in other HIV-positive cohorts and in HIV vaccine trials.
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    PD-1, IL-10, IFN-γ and IL-12 Form a Network to Regulate HIV-1-Specific CD4 T Cell and Antigen-Presenting Cell Function
    (BioMed Central, 2012) Porichis, Filippos; Barblu, Lucie; Kwon, Douglas; Hart, M; Zupkosky, J; Freeman, Gordon; Kavanagh, Daniel Garrett; Kaufmann, Daniel E.
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    A High-Dimensional Immune Monitoring Model of HIV-1-Specific CD8 T Cell Responses Accurately Identifies Subjects Achieving Spontaneous Viral Control
    (BioMed Central, 2012) Proudfoot, J; Vine, S; Cesa, K; Piechocka-Trocha, A; Ndhlovu, Zaza; Chibnik, Lori; McMullen, A; Porichis, Filippos; Alvino, Donna Marie; De Jager, Philip; Walker, Bruce; Kaufmann, Daniel E.
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    P16-08. Combined blockade of the PD-1 and IL-10 pathways synergistically enhance HIV-specific CD4 T cell functions
    (BioMed Central, 2009) Porichis, Filippos; Kwon, DS; Tighe, DP; Pavlik, DF; Kavanagh, Daniel Garrett; Freeman, Gordon; Walker, Bruce; Kaufmann, Daniel E.