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PIGVAC

PIGVAC

  • A plant?produced immunoenhanced pig vaccine against PRRS

A plant?produced immunoenhanced pig vaccine against PRRS (PIGVAC).

The Danish Council for Strategic Research – Grant: DKK 15.199.389

Project period: 01.01.2014 – 31.12.2018.


Project description

Scientific summary

Porcine reproductive respiratory syndrome virus (PRRSV) causes the most important infectious disease in pigs in Denmark and globally. It has high impact on animal welfare and agricultural economics, and the extensive use of antibiotics to control PRRSV-associated respiratory problems may endanger public health. Thus, control of PRRSV is top priority in all pig producing countries. Contrary to most other virus infections, PRRSV persists in the blood for weeks after antibodies are formed due to dominant decoy antigens masking the subdominant epitopes that provide immunity at later stages.

PRRSV is extremely difficult to control as existing vaccine are not effective in preventing infection or excretion of virus. Consensus is that PRRSV can only be controlled by vaccines that are safe, efficacious and rapidly adaptable to prevalent strains. State-of-the-art vaccine research has identified non-infectious subunit vaccines such as virus-like-particles (VLPs) to be the most efficient entities developed to date, triggering both humoral and cellular immune responses.

We propose to alter immunosuppressive motifs in the major target for neutralizing antibodies of PRRSV (GP5) and to produce VLPs presenting the modified GP5 in plants to gain advantages in terms of safety, speed, cost, and efficacy. This poses scientific challenges such as i) membrane presentation of an animal virus protein in plants, ii) association of GP5 with VLPs formed by a cytosol-delivered matrix protein, iii) verification and modification of immunosuppressive domains in GP5, and iv) efficient production. VLPs will be characterized and vaccine efficacy tested in pigs. If successful, the project will provide industrial scale ready proof-of-concept for a novel PRRSV-vaccine and establish a platform technology for future vaccines against e.g. SARS or HIV.

Objective

The overall objective is to develop an efficient, safe and low-cost vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV causes respiratory disorders, reproductive disorders and high mortality in pigslets and is the most important infectious pathogen of swine. Existig vaccines are either not very efficient or very unsafe in use. The major target of neutralizing antiodies against PRRAV and as such the most promising vaccine candidate is the envelope glycoprotein GP5.

In other RNA viruses, envelope proteins have been found to harbor immunosuppresssive domais that counteract host immune responses. Envelope proteins with abrogated immnosuppressive domains show improved vaccine efficacy. Virus-like particles (VLSPs) are known to trigger both a humoral and a cell-mediated immune response, and plant-based production offers advantages in terms of cost, rapid adaptability to emerging strains, scalability and safety. Thus we propose to:

i) knock-out immunosuppressive motifs in GP5
ii) produce VLPs exposing such hyperimmunogenic GP5 in tobacco
iii) test the immunological response to the VLPs in pigs
iv) perform large-scale challenge studies in pigs.


Partners

Aarhus University, Denmark
The Department of Molecular Biology and Genetics
Virus Group

  • Finn Skou Pedersen
  • Mogens Duch
 

The Technical University of Denmark
Center for Electron Nanoscopy

  • Lars Erik Larsen
  • Gregers Jungersen
  • Jakob Birkedal Wagner
 
Aarhus University, Denmark
The Department of Molecular Biology and Genetics
Plant Group

  • Jens Stougaard
  • Stig Uggerhøj Andersen
 
The Technical University of Denmark
The National Veterinary Institute
  • Ramona Valentina Mateiu
 

The Institute of Virology and Immunoprophylaxis
Switzerland
Laboratory of Virology

  • Nicolas Ruggli
  • Artur Summerfield
 

Danish Pig Research Centre, Denmark

  • Poul Bækbo
  • Charlotte Sonne Kristensen



Boehringer Ingelheim Veterinary Research Center, Germany

  • Konrad Stadler

SKAU vaccines, Denmark

  • Shervin Bahrami
  • Peter Wulff

 

 

Project leader

Latest peer-reviewed publications of project leader

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Fighting the most important contagious swine disease in the world

An international team of researchers is determined to develop a new and more effective vaccine against PRRS – the most important contagious swine disease in the world – which annually costs society enormous amounts and leads to poor animal welfare. The Danish Council for Strategic Research has just granted Professor Finn Skou Pedersen DKK 15 million for the project.

Read more about the research