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12. 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

Author

Bernard Verrier, Denys Brand, Isabelle Dimier-Poisson, Munier Séverine, Philippe Roingeard, Josette Pierre, Fleur Aline, Inconnu, Immunologie parasitaire (TOURS UMR IMMUNOLOGIE PARASIT), and Institut National de la Recherche Agronomique (INRA)-Faculte des Sciences Pharmaceutiques

Subjects
Antigenicity, Cellular immunity, Polymers, [SDV]Life Sciences [q-bio], Polyesters, HIV Core Protein p24, chemical and pharmacologic phenomena, 02 engineering and technology, Biology, HIV Antibodies, Cell Line, 03 medical and health sciences, Mice, Immune system, Th2 Cells, Antigen, Adjuvants, Immunologic, Animals, Lactic Acid, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cell Proliferation, AIDS Vaccines, 0303 health sciences, Immunity, Cellular, CD40, General Veterinary, General Immunology and Microbiology, Immunogenicity, Public Health, Environmental and Occupational Health, Dendritic cell, Dendritic Cells, Th1 Cells, 021001 nanoscience & nanotechnology, 3. Good health, Cell biology, Infectious Diseases, Immunology, biology.protein, HIV-1, Mice, Inbred CBA, Molecular Medicine, Cytokines, Nanoparticles, Female, 0210 nano-technology, CD80
Abstract

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.

Published
2009
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