Recombinant Attenuated Salmonella Vaccine (RASV) - 01.09.14

Overview | Description | Applications | Operations | Results | Publications | Imagery

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Science Objectives for Everyone Recombinant attenuated Salmonella vaccine (RASV) evaluates the ability of the space flight platform to accelerate recombinant attenuated Salmonella vaccine development against pneumococcal pneumonia - which causes life-threatening diseases (pneumonia, meningitis, bacteremia) that kill over 10 million people annually, particularly children and elderly who are less responsive to current anti-pneumococcal vaccines. The overall goal of the RASV experiment is to use space flight as an innovative platform to facilitate the design and development of next generation vaccines with improved efficacy and protective immune responses while minimizing unwanted side effects by 1) providing novel gene targets for vaccine improvement and development, and 2) re-formulating existing vaccines. The experiment is a joint collaboration between Arizona State University researchers, Dr. Cheryl Nickerson and Dr. Roy Curtiss III.

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This content was provided by Cheryl A. Nickerson, Ph.D., and is maintained in a database by the ISS Program Science Office.

Experiment Details

OpNom:

Principal Investigator(s)

  • Cheryl A. Nickerson, Ph.D., Arizona State University, Tempe, AZ, United States
  • Co-Investigator(s)/Collaborator(s)
    Information Pending

    Developer(s)
    Information Pending

    Sponsoring Space Agency
    National Aeronautics and Space Administration (NASA)

    Sponsoring Organization
    National Laboratory (NL)

    Research Benefits
    Information Pending

    ISS Expedition Duration
    March 2011 - September 2011

    Expeditions Assigned
    27/28

    Previous ISS Missions
    Information Pending

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    Experiment Description

    Research Overview

    • Even with tremendous advances in medical science, the threat of infectious disease remains a major health problem for the general public. In this regard, diseases like pneumococcal pneumonia caused by Streptococcus pneumoniae, causes life-threatening diseases (pneumonia, meningitis, bacteremia), which kills over 10 million people annually, particularly children and the elderly who are less responsive to current anti-pneumococcal vaccines. Many of these deaths could be prevented by 1) the development of effective new vaccines for mucosal immunization, and 2) improvement of the safety and efficiency of existing live mucosal vaccines that stimulate effective protective mucosal immune responses.


    • Strains of Salmonella, called recombinant attenuated Salmonella vaccine (RASV) strains, have been genetically modified to carry protective antigens against the pathogen S. pneumoniae. These RASV strains are cultured during space flight to induce responses that provide information that will lead to more effective vaccine strains.


    • Based on the results from our previous space flight experiments demonstrating unique space flight-associated alterations in microbial virulence, we hypothesize that the microgravity environment of space flight can be used to accelerate the development of RASV strains as immunizing vectors against infectious disease by 1) enhancing their ability to safely induce a potent and protective immune response, and 2) unveiling novel gene targets to develop new and improve existing vaccine strains. The ability to uniquely manipulate microbial virulence attributes holds exciting potential for genetic engineering of live bacterial vaccine strains that maximize their ability to induce a potent and protective immune response while minimizing their ability to cause illness. Our ultimate goal is to exploit space flight as an innovative and transformative platform to streamline vaccine discovery and increase likelihood of success in the most expensive part of vaccine development-human clinical trials.

    Description

    Even with tremendous advances in medical science, the threat of infectious disease remains a major health problem for the general public. In this regard, pneumococcal pneumonia caused by Streptococcus pneumoniae, causes life-threatening diseases (pneumonia, meningitis, bacteremia), which kills over 10 million people annually, particularly children and the elderly who are less responsive to current anti-pneumococcal vaccines. Many of these deaths could be prevented by 1) the development of effective new vaccines for mucosal immunization, and 2) improvement of the safety and efficiency of existing live mucosal vaccines that stimulate effective protective mucosal immune responses.

    Recombinant attenuated Salmonella vaccine (RASV) evaluates the ability of the space flight platform to accelerate recombinant attenuated Salmonella vaccine development against pneumococcal pneumonia. The overall goal of the RASV experiment is to use space flight as an innovative platform to facilitate the design and development of next generation vaccines with improved efficacy and protective immune responses while minimizing unwanted side effects by 1) providing novel gene targets for vaccine improvement and development, and 2) re-formulating existing vaccines. The experiment is a joint collaboration between Arizona State University researchers, Dr. Cheryl Nickerson and Dr. Roy Curtiss III.

    Strains of Salmonella, called recombinant attenuated Salmonella vaccine (RASV) strains, are genetically modified to carry protective antigens against the pathogen S. pneumoniae. These RASV strains are cultured during space flight to induce responses that provide information that will lead to more effective vaccine strains.

    Based on the results from our previous space flight experiments demonstrating unique space flight-associated alterations in microbial virulence, we hypothesize that the microgravity environment of space flight can be used to accelerate the development of RASV strains as immunizing vectors against infectious disease by 1) enhancing their ability to safely induce a potent and protective immune response, and 2) unveiling novel gene targets to develop new and improve existing vaccine strains. The ability to uniquely manipulate microbial virulence attributes holds exciting potential for genetic engineering of live bacterial vaccine strains that maximize their ability to induce a potent and protective immune response while minimizing their ability to cause illness. Our ultimate goal is to exploit space flight as an innovative and transformative platform to streamline vaccine discovery and increase likelihood of success in the most expensive part of vaccine development-human clinical trials.

    During our RASV experiment, vaccine strain cultures are activated to grow in space for a specific time period and then supplemented during flight with either additional growth media (to maintain cell viability) or an RNA/protein fixative (for gene expression/microarray studies). In each case, the flight culture samples are compared to samples grown under identical conditions on the ground at the Kennedy Space Center, with the exception that they do not fly. The flight and ground samples are loaded from the same bacterial inoculum into specially-designed hardware (called fluid processing apparatuses or FPAs), which are glass tubes composed of a series of compartments that allowed addition of media or fixative to the cultures. Hardware activation and termination times between flight and ground are coordinated via real time communications with the shuttle crew.

    Immediately after shuttle landing at Kennedy Space Center, the viable culture samples are recovered for subsequent immunization and challenge studies in murine models. Viable cultures are also fixed for electron microscopic analysis after landing. Cultures in RNA/protein fixative are used for whole-genome transcriptional microarray and analysis.

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    Applications

    Space Applications

    Our previous space flight studies demonstrated a significant increase in virulence and/or virulence characteristics in bacterial pathogens when cultured during flight, thus increasing the uncertainty of the infection risk to the crew during a space flight mission. Our current space flight experiment provides additional key information that will advance our understanding of alterations that occur in microbial virulence during space flight, and will lead to better countermeasures against infection in future human exploration missions.

    Earth Applications

    The research results from RASV could lead to the development of new and effective vaccines to combat pneumonia and related infections on earth. Further, these vaccines could have fewer side effects, and provide a template for the development of vaccines to combat other infectious diseases.

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    Operations

    Operational Requirements

    RASV is conducted under ambient conditions. It does not require image or data download.

    Operational Protocols

    During the RASV experiment, vaccine strain cultures are activated to grow in space for a specific time period and then supplemented during flight with either additional growth media (to maintain cell viability) or an RNA/protein fixative (for gene expression/microarray studies). In each case, the flight culture samples are compared to samples grown under identical conditions on the ground at the Kennedy Space Center, with the exception that they do not fly. The flight and ground samples are loaded from the same bacterial inoculum into specially-designed hardware (called fluid processing apparatuses or FPAs), which are glass tubes composed of a series of compartments that allowed addition of media or fixative to the cultures. Hardware activation and termination times between flight and ground are coordinated via real time communications with the Shuttle crew.

    Immediately after shuttle landing at Kennedy Space Center, the viable culture samples are recovered for subsequent immunization and challenge studies in murine models. Viable cultures are also fixed for electron microscopic analysis after landing. Cultures in RNA/protein fixative are used for whole-genome transcriptional microarray and analysis.

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    Results/More Information

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    Results Publications

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    Ground Based Results Publications

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    ISS Patents

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    Related Publications

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    Related Websites

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    Imagery

    image NASA Image: S115e07274 - Astronaut Heidemarie M. Stefanyshyn-Piper, Mission Specialist holding the Microbe Group Activation Pack containing eight Fluid Processing Apparatuses in the middeck of the Space Shuttle Atlantis during Expedition 13 and STS-115 joint operations.
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    image NASA image: S123E009086 - Dominic Gorie, STS-123 commander, watches Group Activation Pack (GAP) float, containing Microbial Drug Resistance Virulence (MDRV). Photo was taken during STS-123 / Expedition 16 joint operations.
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    image Cheryl Nickerson of the Biodesign Institute at Arizona State University Image courtesy of Nick Meek.
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