scholarly journals Safety and Tolerability of Conserved Region Vaccines Vectored by Plasmid DNA, Simian Adenovirus and Modified Vaccinia Virus Ankara Administered to Human Immunodeficiency Virus Type 1-Uninfected Adults in a Randomized, Single-Blind Phase I Trial

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e101591 ◽  
Author(s):  
Emma-Jo Hayton ◽  
Annie Rose ◽  
Umar Ibrahimsa ◽  
Mariarosaria Del Sorbo ◽  
Stefania Capone ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Phase I ◽  
Vaccinia Virus ◽  
Plasmid Dna ◽  
Phase I Trial ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Simian Adenovirus ◽  
Single Blind

scholarly journals DNA and Modified Vaccinia Virus Ankara Vaccines Encoding Multiple Cytotoxic and Helper T-Lymphocyte Epitopes of Human Immunodeficiency Virus Type 1 (HIV-1) Are Safe but Weakly Immunogenic in HIV-1-Uninfected, Vaccinia Virus-Naive Adults

2012 ◽  
Vol 19 (5) ◽  
pp. 649-658 ◽  
Author(s):  
Geoffrey J. Gorse ◽  
Mark J. Newman ◽  
Allan deCamp ◽  
Christine Mhorag Hay ◽  
Stephen C. De Rosa ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Lymphocyte ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACTWe evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia virus Ankara vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double-blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a heterologous prime-boost schedule. HIV-1-specific cellular immune responses, measured as interleukin-2 and/or gamma interferon production, were induced in 1 (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25 subjects after the second MVA-mBN32 immunization. Among these responders, polyfunctional T-cell responses, including the production of tumor necrosis factor alpha and perforin, were detected. Vaccinia virus-specific antibodies were induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the first and second immunizations with MVA-mBN32. These peptide-based vaccines were safe but were ineffective at inducing HIV-1-specific immune responses and induced much weaker responses than MVA vaccines expressing the entire open reading frames of HIV-1 proteins.

scholarly journals Attenuated Modified Vaccinia Virus Ankara Can Be Used as an Immunizing Agent under Conditions of Preexisting Immunity to the Vector

2000 ◽  
Vol 74 (16) ◽  
pp. 7651-7655 ◽  
Author(s):  
Juan C. Ramírez ◽  
M. Magdalena Gherardi ◽  
Dolores Rodríguez ◽  
Mariano Esteban
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Human Immunodeficiency Virus Type ◽  
Human Population ◽  
Cellular Immune Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Cellular Immune

ABSTRACT A problem associated with the use of vaccinia virus recombinants as vaccines is the existence of a large human population with preexisting immunity to the vector. Here we showed that after a booster with attenuated recombinant modified vaccinia virus Ankara (rMVA), higher humoral and cellular immune responses to foreign antigens (human immunodeficiency virus type 1 Env and β-galactosidase) were found in mice preimmunized with rMVA than in mice primed with the virulent Western Reserve strain and boosted with rMVA. This enhancement correlated with higher levels of expression of foreign antigens after the booster.

scholarly journals Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction

2007 ◽  
Vol 88 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Tomáš Hanke ◽  
Andrew J. McMichael ◽  
Lucy Dorrell
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Vaccinia Virus ◽  
T Cell Responses ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Cell Induction ◽  
Hiv 1

Candidate human immunodeficiency virus type 1 (HIV-1) vaccines focusing on T-cell induction, constructed as pTHr.HIVA DNA and modified vaccinia virus Ankara (MVA).HIVA, were delivered in a heterologous prime–boost regimen. The vaccines were tested in several hundred healthy or HIV-1-infected volunteers in Europe and Africa. Whilst larger trials of hundreds of volunteers suggested induction of HIV-1-specific T-cell responses in <15 % of healthy vaccinees, a series of small, rapid trials in 12–24 volunteers at a time with a more in-depth analysis of vaccine-elicited T-cell responses proved to be highly informative and provided more encouraging results. These trials demonstrated that the pTHr.HIVA vaccine alone primed consistently weak and mainly CD4+, but also CD8+ T-cell responses, and the MVA.HIVA vaccine delivered a consistent boost to both CD4+ and CD8+ T cells, which was particularly strong in HIV-1-infected patients. Thus, whilst the search is on for ways to enhance T-cell priming, MVA is a useful boosting vector for human subunit genetic vaccines.

scholarly journals Expansion and Diversification of Virus-Specific T Cells following Immunization of Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals with a Recombinant Modified Vaccinia Virus Ankara/HIV-1 Gag Vaccine

2006 ◽  
Vol 80 (10) ◽  
pp. 4705-4716 ◽  
Author(s):  
Lucy Dorrell ◽  
Hongbing Yang ◽  
Beatrice Ondondo ◽  
Tao Dong ◽  
Kati di Gleria ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Vaccinia Virus ◽  
Human Immunodeficiency Virus Type ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Affordable therapeutic strategies that induce sustained control of human immunodeficiency virus type 1 (HIV-1) replication and are tailored to the developing world are urgently needed. Since CD8+ and CD4+ T cells are crucial to HIV-1 control, stimulation of potent cellular responses by therapeutic vaccination might be exploited to reduce antiretroviral drug exposure. However, therapeutic vaccines tested to date have shown modest immunogenicity. In this study, we performed a comprehensive analysis of the changes in virus-specific CD8+ and CD4+ T-cell responses occurring after vaccination of 16 HIV-1-infected individuals with a recombinant modified vaccinia virus Ankara-vectored vaccine expressing the consensus HIV-1 clade A Gag p24/p17 sequences and multiple CD8+ T-cell epitopes during highly active antiretroviral therapy. We observed significant amplification and broadening of CD8+ and CD4+ gamma interferon responses to vaccine-derived epitopes in the vaccinees, without rebound viremia, but not in two unvaccinated controls followed simultaneously. Vaccine-driven CD8+ T-cell expansions were also detected by tetramer reactivity, predominantly in the CD45RA− CCR7+ or CD45RA− CCR7− compartments, and persisted for at least 1 year. Expansion was associated with a marked but transient up-regulation of CD38 and perforin within days of vaccination. Gag-specific CD8+ and CD4+ T-cell proliferation also increased postvaccination. These data suggest that immunization with MVA.HIVA is a feasible strategy to enhance potentially protective T-cell responses in individuals with chronic HIV-1 infection.

scholarly journals Induction of Potent Human Immunodeficiency Virus Type 1-Specific T-Cell-Restricted Immunity by Genetically Modified Dendritic Cells

2001 ◽  
Vol 75 (16) ◽  
pp. 7621-7628 ◽  
Author(s):  
Julianna Lisziewicz ◽  
Dmitry I. Gabrilovich ◽  
Georg Varga ◽  
Jianqing Xu ◽  
Philip D. Greenberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Plasmid Dna ◽  
Genetically Modified ◽  
Ctl Response ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A novel technology combining replication- and integration-defective human immunodeficiency virus type 1 (HIV-1) vectors with genetically modified dendritic cells was developed in order to induce T-cell immunity. We introduced the vector into dendritic cells as a plasmid DNA using polyethylenimine as the gene delivery system, thereby circumventing the problem of obtaining viral vector expression in the absence of integration. Genetically modified dendritic cells (GMDC) presented viral epitopes efficiently, secreted interleukin 12, and primed both CD4+ and CD8+ HIV-specific T cells capable of producing gamma interferon and exerting potent HIV-1-specific cytotoxicity in vitro. In nonhuman primates, subcutaneously injected GMDC migrated into the draining lymph node at an unprecedentedly high rate and expressed the plasmid DNA. The animals presented a vigorous HIV-specific effector cytotoxic-T-lymphocyte (CTL) response as early as 3 weeks after a single immunization, which later developed into a memory CTL response. Interestingly, antibodies did not accompany these CTL responses, indicating that GMDC can induce a pure Th1 type of immune response. Successful induction of a broad and long-lasting HIV-specific cellular immunity is expected to control virus replication in infected individuals.

scholarly journals A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans

2004 ◽  
Vol 85 (4) ◽  
pp. 911-919 ◽  
Author(s):  
Matilu Mwau ◽  
Inese Cebere ◽  
Julian Sutton ◽  
Priscilla Chikoti ◽  
Nicola Winstone ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Vaccinia Virus ◽  
Mononuclear Cells ◽  
Vaccine Development ◽  
Cell Mediated Immunity ◽  
Phase I Clinical Trials ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Hiv 1

The immunogenicities of candidate DNA- and modified vaccinia virus Ankara (MVA)-vectored human immunodeficiency virus (HIV) vaccines were evaluated on their own and in a prime–boost regimen in phase I clinical trials in healthy uninfected individuals in the United Kingdom. Given the current lack of approaches capable of inducing broad HIV-neutralizing antibodies, the pTHr.HIVA DNA and MVA.HIVA vaccines focus solely on the induction of cell-mediated immunity. The vaccines expressed a common immunogen, HIVA, which consists of consensus HIV-1 clade A Gag p24/p17 proteins fused to a string of clade A-derived epitopes recognized by cytotoxic T lymphocytes (CTLs). Volunteers' fresh peripheral blood mononuclear cells were tested for HIV-specific responses in a validated gamma interferon enzyme-linked immunospot (ELISPOT) assay using four overlapping peptide pools across the Gag domain and three pools of known CTL epitopes present in all of the HIVA protein. Both the DNA and the MVA vaccines alone and in a DNA prime–MVA boost combination were safe and induced HIV-specific responses in 14 out of 18, seven out of eight and eight out of nine volunteers, respectively. These results are very encouraging and justify further vaccine development.

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