Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans

  title={Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans},
  author={Samuel McConkey and William H. H. Reece and Vasee Moorthy and Daniel P. Webster and Susanna J . Dunachie and Geoffrey A. Butcher and Jenni M. Vuola and Tom J. Blanchard and Philip Gothard and Katherine R Watkins and Carolyn M. Hannan and Simone Everaere and Karen Brown and Kent E. Kester and James F. Cummings and Jackie Williams and Donald Gray Heppner and Ansar Pathan and Katie L. Flanagan and Nirmalan Arulanantham and Mark Roberts and M J Roy and Geoffrey L. Smith and Joerg Schneider and Tim E. A. Peto and Robert E Sinden and Sarah C. Gilbert and Adrian V. S. Hill},
  journal={Nature Medicine},
In animals, effective immune responses against malignancies and against several infectious pathogens, including malaria, are mediated by T cells. Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally, followed by intradermal recombinant modified vaccinia virus Ankara (MVA), induces high frequencies of interferon (IFN)-γ-secreting, antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen, thrombospondin-related… 

Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara.

  • D. WebsterS. Dunachie A. Hill
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
It is reported that substitution of plasmid DNA as the priming vector with a specific attenuated recombinant fowlpox virus, FP9, vaccine in such prime-boost regimes can elicit complete sterile protection that can last for 20 months.

Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans

Recombinant modified vaccinia virus Ankara expressing antigen 85A (MVA85A) was found to induce high levels of antigen-specific IFN-γ-secreting T cells when used alone in bacille Calmette-Guérin (BCG)-naive healthy volunteers.

Differential Immunogenicity of Various Heterologous Prime-Boost Vaccine Regimens Using DNA and Viral Vectors in Healthy Volunteers1

Describing cell-mediated immune responses induced by different prime-boost combinations where all vectors encode a multiepitope string fused to the pre-erythrocytic Ag thrombospondin-related adhesion protein shows that these different vectors need to be used in a specific order for an optimal ex vivo IFN-γ response.

Progress in DNA‐based heterologous prime‐boost immunization strategies for malaria

In these clinical trials, remarkably high levels of effector T‐cell responses have been induced and significant protection documented in a human sporozoite challenge model, and encouraging results that have been observed in vaccinated humans.

Prime-boost strategies in DNA vaccines.

This chapter describes the use of prime-boost vaccines to induce T-cell responses against HIV-1 and protective immunity against AIDS in macaques.

Prime boost regimens for enhancing immunity: magnitude, quality of mucosal and systemic gene vaccines

This chapter discusses the use of gene based heterologous prime-boost immunisation strategies for improved vaccination against intracellular pathogens, particularly with respect to HIV-1, given that prime- boost vaccine strategies have been extensively tested and studied against this virus in animal models as well as in humans.

A DNA Vaccine Prime Followed by a Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses and Protection1

Results support the conclusion that this new approach is capable of generating a Th-type-1-biased, broad spectrum immune response, specifically at mucosal surfaces, and may provide a safe and effective vaccination alternative for human use.

Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation

It is demonstrated that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP, providing protection against human malaria.



Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara

DNA priming followed by MVA boosting may provide a general immunization regime for induction of high levels of CD8+ T cells and was abrogated when the order of immunization was reversed.

Enhanced Immunogenicity of CD4+ T-Cell Responses and Protective Efficacy of a DNA-Modified Vaccinia Virus Ankara Prime-Boost Vaccination Regimen for Murine Tuberculosis

Heterologous prime-boost regimens boost CD4+ as well as CD8+T-cell responses, and the use of heterologous constructs encoding the same antigen(s) may improve the immunogenicity and protective efficacy of DNA vaccines against tuberculosis and other diseases.

Protection from Plasmodium berghei infection by priming and boosting T cells to a single class I‐restricted epitope with recombinant carriers suitable for human use

The novel recombinant Ty/MVA prime/boost combination with these constructs provides a safe alternative for evaluation for human vaccination against P. falciparum malaria.

Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine.

This first demonstration in healthy naïve humans of the induction of CD8+ C TLs by DNA vaccines, including CTLs that were restricted by multiple HLA alleles in the same individual, provides a foundation for further human testing of this potentially revolutionary vaccine technology.

Induction of CD4+ T cell-dependent CD8+ type 1 responses in humans by a malaria DNA vaccine

Demonstration in humans of elicitation of the class I restricted IFN-γ responses the authors believe necessary for protection against the liver stage of malaria parasites brings us closer to an effective malaria vaccine.