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Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC.
Kibler, Karen V; Asbach, Benedikt; Perdiguero, Beatriz; García-Arriaza, Juan; Yates, Nicole L; Parks, Robert; Stanfield-Oakley, Sherry; Ferrari, Guido; Montefiori, David C; Tomaras, Georgia D; Roederer, Mario; Foulds, Kathryn E; Forthal, Donald N; Seaman, Michael S; Self, Steve; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, James; Barnett, Susan; Cristillo, Anthony D; Weiss, Deborah; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L; Esteban, Mariano; Wagner, Ralf; Pantaleo, Giuseppe; Jacobs, Bertram L.
Afiliação
  • Kibler KV; Biodesign Institute, Arizona State University, Tempe, Arizona, USA.
  • Asbach B; Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
  • Perdiguero B; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • García-Arriaza J; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • Yates NL; Duke University Medical Center, Durham, North Carolina, USA.
  • Parks R; Duke University Medical Center, Durham, North Carolina, USA.
  • Stanfield-Oakley S; Duke University Medical Center, Durham, North Carolina, USA.
  • Ferrari G; Duke University Medical Center, Durham, North Carolina, USA.
  • Montefiori DC; Duke University Medical Center, Durham, North Carolina, USA.
  • Tomaras GD; Duke University Medical Center, Durham, North Carolina, USA.
  • Roederer M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Foulds KE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Forthal DN; Division of Infectious Diseases Department of Medicine, University of California, Irvine School of Medicine, Irvine, California, USA.
  • Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
  • Self S; Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Gottardo R; Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Phogat S; Sanofi Pasteur, Swiftwater, Pennsylvania, USA.
  • Tartaglia J; Sanofi Pasteur, Swiftwater, Pennsylvania, USA.
  • Barnett S; Novartis Vaccines and Diagnostics, Inc., Cambridge, Massachusetts, USA.
  • Cristillo AD; Advanced BioScience Laboratories, Inc., Rockville, Maryland, USA.
  • Weiss D; Advanced BioScience Laboratories, Inc., Rockville, Maryland, USA.
  • Galmin L; Advanced BioScience Laboratories, Inc., Rockville, Maryland, USA.
  • Ding S; EuroVacc Foundation, Lausanne, Switzerland.
  • Heeney JL; Lab of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
  • Esteban M; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
  • Wagner R; Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
  • Pantaleo G; Institute of Clinical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
  • Jacobs BL; Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
J Virol ; 93(3)2019 02 01.
Article em En | MEDLINE | ID: mdl-30429340
As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here, we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a nonhuman primate study, which utilized a prime-boost regimen similar to that of RV144. NYVAC-C and NYVAC-C-KC express the HIV-1 antigens gp140, and Gag/Gag-Pol-Nef-derived virus-like particles (VLPs) from clade C and were used as the prime, with recombinant virus plus envelope protein used as the boost. In nearly every T and B cell immune assay against HIV-1, including neutralization and antibody binding, NYVAC-C-KC induced a greater immune response than NYVAC-C, indicating that replication competence in a poxvirus may improve upon the modestly successful regimen used in the RV144 clinical trial.IMPORTANCE Though the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells, similar to the ALVAC vector used in RV144. We have utilized a prime-boost regimen for administration of the vaccine candidate that is similar to the one used in the RV144 study. The results of this study indicate that a replication-competent poxvirus vector may improve upon the effectiveness of the RV144 clinical trial vaccine candidate.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Replicação Viral / Vacinas Virais / Antígenos HIV / Linfócitos T CD4-Positivos / Infecções por HIV / HIV-1 / Produtos do Gene env do Vírus da Imunodeficiência Humana Tipo de estudo: Clinical_trials Limite: Animals / Humans / Male Idioma: En Revista: J Virol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Replicação Viral / Vacinas Virais / Antígenos HIV / Linfócitos T CD4-Positivos / Infecções por HIV / HIV-1 / Produtos do Gene env do Vírus da Imunodeficiência Humana Tipo de estudo: Clinical_trials Limite: Animals / Humans / Male Idioma: En Revista: J Virol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos