Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models.
Microparticles and nanoparticles prepared with poly(D,L-lactide-co-glycolide) (PLGA) or poly(D,L-lactide) (PLA) polymers represent a promising method for in vivo delivery of encapsulated peptide, protein or DNA antigens. However, one major issue that limits the potential of these delivery systems is the instability or the degradation of the entrapped antigen. Charged microparticles carrying surface adsorbed antigen were developed to resolve this problem and appear more suitable for vaccine applications. We describe here new anionic PLA nanoparticles obtained by the dialysis method that are absolutely surfactant-free, which makes them more appropriate for use in humans. The potency of this delivery system as a vaccine carrier was tested in various animal models using HIV-1 p24 protein. p24-coated PLA nanoparticles (p24/PLA) induced high antibody titres (>10(6)) in mice, rabbits and macaques. Moreover, p24/PLA nanoparticles elicited strong CTL responses and a Th1-biased cytokine release (IFNgamma, IL-2) in mice. p24 protein seemed to generate a more Th1-oriented response when administered coated onto the surface of PLA nanoparticles than adjuvanted with Freund's adjuvant. Most importantly, the ability of p24/PLA particles to induce Th1 responses was also confirmed in the macaque model, since high levels of IFNgamma-producing CD4+ T cells and CD8+ T cells could be detected by the ELISPOT assay. This protein delivery system confirms the potential of charged nanoparticles in the field of vaccine development.
FRE2736 CNRS-bioMérieux, IFR128 BioSciences Lyon-Gerland, Tour CERVI, 21, Avenue Tony Garnier, F-69365 Lyon 07, France.
Yasemin
Y
Ataman-Onal
Séverine
S
Munier
Arnaud
A
Ganée
Céline
C
Terrat
Pierre-Yves
PY
Durand
Nicole
N
Battail
Frédéric
F
Martinon
Roger
R
Le Grand
Marie-Hélène
MH
Charles
Thierry
T
Delair
Bernard
B
Verrier
D000818:Animals; D000838:Anions; D000917:Antibody Formation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D016655:HIV Core Protein p24 / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures; D011091:Polyesters / Q000737:chemistry*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D013501:Surface-Active Agents / Q000737:chemistry; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014611:Vaccination / Q000379:methods
D000838:Anions; D016207:Cytokines; D016655:HIV Core Protein p24; D011091:Polyesters; D011994:Recombinant Proteins; D013501:Surface-Active Agents; C033616:poly(lactide)