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.
Biodegradable nanoparticles with surface adsorbed antigens represent a promising method for in vivo delivery of vaccines targeting a wide range of infectious diseases or cancers. We investigated the feasibility of loading dendritic cells with a vaccine antigen, HIV p24 protein, on the surface of surfactant-free anionic (d,l-lactic acid, PLA) nanoparticles. The p24 protein had a high affinity for the nanoparticles and the antigenicity and immunogenicity of the p24 protein on the nanoparticle was well preserved after immunization. p24-coated nanoparticles were efficiently taken up by mouse dendritic cells (DCs), inducing DC maturation by increasing MHC-I, MHC-II, CD40, CD80 and CD86 surface expression and secreting IL-12 (p70) and IL-4. We evaluated the ability of DCs pulsed with p24-coated nanoparticles to elicit an optimal humoral and cellular immune response in the blood and intestine. DCs pulsed with p24-nanoparticles induced high seric and mucosal antibody production and elicited strong systemic and local lymproliferative responses, correlated with a Th1/Th2-type response, and systemic CTL responses in mice. Thus, DCs pulsed with antigen-loaded PLA nanoparticles may provide a novel delivery tool for cell therapy vaccination against chronic infectious diseases.
Aline
Fleur
F
Université François Rabelais Tours, INRA, UMR 0483 Université-INRA d'Immunologie Parasitaire et Vaccinologie, Biothérapies anti-infectieuses, IFR agents transmissibles en Infectiologie; UFR des Sciences Pharmaceutiques, 37200 Tours, France.
Brand
Denys
D
Pierre
Josette
J
Roingeard
Philippe
P
Séverine
Munier
M
Verrier
Bernard
B
Dimier-Poisson
Isabelle
I
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D016655:HIV Core Protein p24 / Q000008:administration & dosage / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D007111:Immunity, Cellular; D019344:Lactic Acid / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D053758:Nanoparticles; D011091:Polyesters; D011108:Polymers; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)