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

  title={Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara},
  author={Jörg Schneider and Sarah C. Gilbert and Tom J. Blanchard and Tom{\'a}{\vs} Hanke and Kathryn Robson and Carolyn M. Hannan and Marion M. Becker and Robert E Sinden and Geoffrey L. Smith and Adrian V. S. Hill},
  journal={Nature Medicine},
Immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. A particular sequence of subunit immunization with pre-erythrocytic antigens of Plasmodium berghei, consisting of single dose priming with plasmid DNA followed by a single boost with a recombinant modified vaccinia virus Ankara (MVA) expressing the same antigen, induced unprecedented complete protection against P. berghei sporozoite… 

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

It is shown 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-γ-secreting, antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen, thrombospondin-related adhesion protein (TRAP).

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.

Induction of Protective Immunity against Malaria by Priming-Boosting Immunization with Recombinant Cold-Adapted Influenza and Modified Vaccinia Ankara Viruses Expressing a CD8+-T-Cell Epitope Derived from the Circumsporozoite Protein of Plasmodium yoelii

This is the first time that the vaccine efficacy of a recombinant cold-adapted influenza virus vector expressing a foreign antigen has been evaluated and elicited high levels of protection against malaria.

Ty Virus-Like Particles, DNA Vaccines and Modified Vaccinia Virus Ankara; Comparisons and Combinations

This method of vaccination uses delivery systems and routes that can be used in humans and could provide a generally applicable regime for the induction of high levels of CD8+ T cells.

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.

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.

Safety, Immunogenicity, and Efficacy of Prime-Boost Immunization with Recombinant Poxvirus FP9 and Modified Vaccinia Virus Ankara Encoding the Full-Length Plasmodium falciparum Circumsporozoite Protein

A series of trials assessing recombinant fowlpox virus and modified vaccinia virus Ankara encoding the Plasmodium falciparum circumsporozoite protein in various prime-boost combinations, doses, and application routes showed no evidence of efficacy in a sporozoite challenge.

Heterologous Priming-Boosting Immunization of Cattle with Mycobacterium tuberculosis 85A Induces Antigen-Specific T-Cell Responses

It appears that intradermal priming was more effective than intramuscular delivery of the priming dose for boosting with the modified vaccinia virus Ankara strain in cattle, suggesting that the method may be useful for development of veterinary vaccines.



Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria.

  • S. LiM. Rodrigues F. Zavala
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
This work generated a recombinant influenza virus expressing an epitope from the circumsporozoite protein of P. yoelii known to be recognized by CD8+ T cells and demonstrated that this vector induced class I major histocompatibility complex-restricted cytotoxic T cells against this foreign epitope.

Host range restricted, non-replicating vaccinia virus vectors as vaccine candidates.

The potential usefulness of recombinant MVA for prophylactic vaccination and therapeutic treatment of infectious diseases and cancer is suggested and previous data on the safety of MVA in humans is suggested.

Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein.

The utility of plasmid DNA immunization against a nonviral infection is demonstrated and this method of immunization provides an important alternative for rapid identification of protective B- and T-cell epitopes and for construction of vaccines to prevent malaria and other infectious diseases.

Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein.

Mice immunized with P815 cells that had been transfected with either SSP2 or CS genes were partially protected, and those immunization with a mixture of S SP2 and CS transfectants were completely protected against malaria.

Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon gamma-, and nitric oxide-dependent immunity

It is reported that immunization with plasmid DNA encoding the plasmodium yoelii circumsporozoite protein protected one of five strains of mice against malaria and introduced a new target of protective preerythrocytic immune responses, PyHEP 17 and its P. falciparum homologue.

Oral immunization with a replication-deficient recombinant vaccinia virus protects mice against influenza

It is found that the vaccine enhanced recovery from infection caused by a shifted (H3N2) influenza virus, probably through the induction of nucleoprotein-specific cytotoxic T-lymphocyte activity.

Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity.

Findings support the concept that live viral vectors expressing the appropriate proteins and/or epitopes can be used as promising vaccine candidates.

Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells

It is reported that a vaccinia virus recombinant, expressing the influenza HA, primes and stimulates a specific murine cytotoxic T-lymphocyte (CTL) response and Histocompatible cells infected with this recombinant also serve as targets for CTLs.

Recombinant polyepitope vaccines for the delivery of multiple CD8 cytotoxic T cell epitopes.

An artificial "polyepitope" protein containing 10 contiguous minimal CTL epitopes, which were restricted by five MHC alleles and derived from five viruses, a parasite, and a tumor model, which should find application in CTL-based vaccine design.

Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria

PROTECTIVE immunity against malaria is induced by vaccination of hosts with irradiation-attenuated sporozoites. This immunity is mediated in part by neutralizing antibodies that are directed mainly