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Accueil du site > Equipes > Vecteurs colloïdaux et transport tissulaire (B. Verrier) > Thématiques > Vaccins particulaires et évaluations thérapeutiques > Particulate vaccines and therapeutic evaluations

Particulate vaccines and therapeutic evaluations

Project leader(s) : B. Verrier, C. Primard.

People involved in the project : P. Mercier, V. Pavot, C. Terrat, M. Berthet.

Particulate vaccines based on poly(D,L-lactic acid) (PLA) are prepared using solvent diffusion method, a one-step and surfactant-free process. The PLA nanoparticles are versatile carriers able to deliver molecules of different nature, encapsulated or adsorbed onto their surface. We have already encapsulated different drugs such as antiretrovirals, ligands or anti-cancer compounds and also adsorbed onto their surface one or more antigens (proteins, nucleic acids …). Moreover the addition of immunostimulatory molecules (TLR ligands, Nods ligands) can significantly increase their immunogenicity. Thus, we can elaborate more or less complex formulations based on a simple association between nanoparticles and antigen. According to the choice of the vaccine antigen we can develop on demand formulation depending on the immune response expected, either predominantly humoral, cellular or mucosal. Thus, such formulations can be tested against many infectious diseases including HIV-1, the main disease model HIV-1of our lab.

These different formulations are evaluated by different panel of experiments to decipher their immune properties :
i) by their ability to activate dendritic cells, in vitro
ii) By immunizing mice or rabbits and follow up of the cellular, humoral and mucosal immune responses.
iii) By testing different challenge models through collaborations with partners involved in national (ANR) and European (CUT’HIVAC, FP7, Munanovac, Europrise) projects.

Lastly, we can compare and test new routes of immunization (topical, oral) and innovative concepts of heterologous prime/boost vaccination protocols to increase the immune responses. For instance, PLA nanoparticles have been used in combination with viral vectors uch as MVA (Modified Vaccinia virus Ankara) poxvirus, eliciting strong, broad and long lasting immune responses.

Accumulation of PLA nanoparticles in endosomal compartments of mouse dendritic cells (SRDC).

References :

Encapsulation of Nod1 and Nod2 receptor ligands into poly(lactic acid) nanoparticles potentiates their immune properties.
Pavot V, Rochereau N, Primard C, Genin C, Perouzel E, Lioux T, Paul S, Verrier B.
(2013) J Control Release 167(1):60-7.

Intradermal Immunization Triggers Epidermal Langerhans Cell Mobilization Required for CD8 T-Cell Immune Responses.
Liard C, Munier S, Joulin-Giet A, Bonduelle O, Hadam S, Duffy D, Vogt A, Verrier B, Combadière B.
(2012) J Invest Dermatol 
132(3 Pt 1):615-25 

Targeting of HIV-p24 particle-based vaccine into differential skin layers induces distinct arms of the immune responses.
Liard C, Munier S, Arias M, Joulin-Giet A, Bonduelle O, Duffy D, Shattock RJ, Verrier B, Combadière B
(2011) Vaccine 26 ;29(37):6379-91

New Insights In Mucosal Vaccine Development.
Pavot V, Rochereau N, Genin C, Verrier B, Paul S
(2012) Vaccine 

Dendritic cells loaded with HIV-1 p24 proteins adsorbed on surfactant-free anionic PLA nanoparticles induce enhanced cellular immune responses against HIV-1 after vaccination.
Aline F, Brand D, Pierre J, Roingeard P, Munier S, Verrier B, Dimier-Poisson I.
(2009) Vaccine 27(38):5284-91.

Formulation Of Hiv-1 Tat And P24 Antigens By Pla Nanoparticles Or Mf59 Impacts The Breadth, But Not The Magnitude, Of Serum And Faecal Antibody Responses In Rabbits.
Guillon C, Mayol K, Terrat C, Compagnon C, Primard C, Charles MH, Delair T, Munier S, Verrier B
(2007) Vaccine 25 : 7491-501

Design And Characterization Of An Hiv-1 Tat Mutant : Inactivation Of Viral And Cellular Functions But Not Antigenicity.
Mayol K, Munier S, Beck A, Verrier B, Guillon C
(2007) Vaccine 25 : 6047-60

Surfactant-free Anionic Pla Nanoparticles Coated With Hiv-1 P24 Protein Induced Enhanced Cellular And Humoral Immune Responses In Various Animal Models.
Ataman-Onal Y, Munier S, Ganee A, Terrat C, Durand PY, Battail N, Martinon F, Le Grand R, Charles MH, Delair T, Verrier B
(2006) J Control Release 112 : 175-85

Coadsorption Of Hiv-1 P24 And Gp120 Proteins To Surfactant-free Anionic Pla Nanoparticles Preserves Antigenicity And Immunogenicity.
Lamalle-Bernard D, Munier S, Compagnon C, Charles MH, Kalyanaraman VS, Delair T, Verrier B, Ataman-Onal Y
(2006) J Control Release 115 : 57-67

Collaborations and financial supports :

Pr. Stéphane PAUL & Pr. Christian GENIN
Groupe Immunité des Muqueuses et Agents Pathogènes, GIMAP
Faculté de Médecine Jacques Lisfranc
15, rue Ambroise Paré
42023 Saint-Etienne Cedex 2, France

Jean-Nicolas TOURNIER & Yves-Pierre GAUTHIER
Centre de Recherches du Service de Santé des Armées, CRSSA

24 Avenue des Maquis du Grésivaudan
38702 LA TRONCHE CEDEX, France

ADITEC : Advanced Immunization Technologies
Coordinator : Dr. Ali Harandi
Department of Microbiology and Immunology
Institute of Biomedicine, University of Gothenburg

Medicinaregatan 7A
41390 Gothenburg, Suède

Cuthivac : Cutaneous and Mucosal HIV Vaccination
Coordinator : Dr. Behazine COMBADIERE
Université Pierre et Marie Curie et INSERM

Paris, France

Europrise : European Vaccines and Microbicides Enterprise
Coordinator : Pr. Robin Shattock
St-Georges University
London, UK

iNanoDCs : Design of multifunctional nanoparticles targeting TLR or Nod receptors for dendritic cell immune therapy
Coordinator : Dr. Bernard VERRIER
IBCP - UMR 5305
Lyon, France