PhD PROPOSAL FOR THE PASTEUR-PARIS UNIVERSITY INTERNATIONAL PROGRAM

 

Deadline for full application: December 15th, 2013

Interviews: March, 2014

Start of the Ph.D.: October 1st, 2014

 

Department: Virology

Title of the PhD project: A subunit vaccine platform based on viral nanoparticles as carrier of heterelogous antigens.

Name of the lab: Unité de Génomique Virale et Vaccination (UG2V)

Head of the lab: Frédéric Tangy

PhD advisor: Monica Sala

Email address: joo@pasteur.fr

Web site address of the lab: http://www.pasteur.fr/ip/easysite/pasteur/fr/recherche/departements-scie...

Doctoral school affiliation and University: B3MI; Paris V and Paris VII Universities.

 

Presentation of the laboratory and its research topics:

The UG2V is dedicated to vaccine design using recombinant live vectors against arboviruses and HIV. The Unit also works on the identification of antiviral compounds targeting virus-host protein interactions. Dr M Sala, group leader in the Unit, develops a new vaccine platform based on recombinant yeast expressing viral nanoparticles engineered to expose on their surface various vaccine antigens relevant for major human diseases (i.e. malaria, viral encephalitis, etc).

 

Description of the project:

Yeasts are largely used as bioreactors for vaccine production. Usually, antigens are produced in yeast, then purified and mixed with adjuvants before immunization. However, the purification costs and the safety concerns recently raised by the use of new adjuvants argue for alternative strategies. To this end, the use of whole yeast as both production and delivery system appears attractive. Indeed, whole yeast-based vaccines are able to elicit both humoral and cell-mediated immune responses in the absence of adjuvants. We developed an original strategy to deliver antigens by expressing viral nanoparticles inside whole recombinant yeast to further increase antigen adjuvancy. We tested this new vaccine strategy in a highly stringent mouse malaria model: C57Bl/6 mice challenged by Plasmodium berghei (Pb). Subcutaneous immunization with whole recombinant heat-inactivated Pichia pastoris yeast expressing the major surface antigen (CS) of Pb provided significant protection against intradermal challenge with a high dose of parasites and significantly decreased clinical damages. This new vaccine formulation is applicable for large-scale production, distribution and delivery in developing countries. A patent application and a scientific article have been recently filed to describe this new approach.

 

The proposed project aims at: i) increasing the adjuvancy of this new vaccine platform by yeast biotechnology; ii) testing the efficiency of this vaccine strategy towards enterovirus infection following oral administration; iii) assessing multivalent vaccine formulation by mixing whole recombinant yeasts expressing different antigens.

 

References:

  • Brandler S et al, JID 2012.
  • Kostrzak A et al, Vaccine 2009.

 

Keywords: Viral vaccine, heat-inactivated yeast, viral nanoparticles, vaccine delivery.

 

Expected profile of the candidate (optional): A background in some of the following fields would be appreciated: molecular and cellular biology, yeast biology, mouse animal model, basic immunology techniques. Applicants should be fluent in English.

 

Contact: Monica Sala (joo@pasteur.fr)

Mis à jour le 16/09/2013