title: 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.
abstract: Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines. Here we used a rabbit model to compare quantitatively and qualitatively the antibody responses induced by poly(D,L-lactide) nanoparticles (PLA) and by emulsion adjuvant MF59 using three HIV-1 antigens: p24gag, WT Tat and a mutated, detoxified form of Tat. We could show that all antigens and adjuvants lead to the induction of similar level of IgG titres in serum when injected subcutaneously. p24, but not Tat, could also induce faecal IgG in rabbits when formulated with PLA or MF59. The nature of the adjuvant had consequences on the spectrum of specificity induced, depending on the antigen: PLA adjuvant focussed the anti-p24 response to an immunodominant domain when compared to MF59. With wild-type Tat, no difference between adjuvants was observed in the spectrum of specificity induced. On the opposite, detoxified Tat coated on PLA increased the number of epitopes recognized by serum IgG compared to MF59 adjuvantation. The impact of these qualitative differences depending on the antigen/adjuvant associations will be important to take into account for further designs of vaccinal formulation using particulate adjuvants.
authors: FRE2736 CNRS/bioMérieux, IFR128 BioSciences Gerland-Lyon Sud, 21 avenue Tony Garnier, 69007 Lyon, France. c.guillon@ibcp.fr
authors: Christophe
authors: C
authors: Guillon
authors: Katia
authors: K
authors: Mayol
authors: Céline
authors: C
authors: Terrat
authors: Christelle
authors: C
authors: Compagnon
authors: Charlotte
authors: C
authors: Primard
authors: Marie-Hélène
authors: MH
authors: Charles
authors: Thierry
authors: T
authors: Delair
authors: Séverine
authors: S
authors: Munier
authors: Bernard
authors: B
authors: Verrier
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry; D015696:Gene Products, tat / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry*; D011817:Rabbits; D013185:Squalene / Q000737:chemistry*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D015696:Gene Products, tat; D016655:HIV Core Protein p24; C089950:MF59 oil emulsion; D011091:Polyesters; D011136:Polysorbates; C033616:poly(lactide); D013185:Squalene