title: Induction of humoral and enhanced cellular immune responses by novel core-shell nanosphere- and microsphere-based vaccine formulations following systemic and mucosal administration.
abstract: Anionic surfactant-free polymeric core-shell nanospheres and microspheres were previously described with an inner core constituted by poly(methylmethacrylate) (PMMA) and a highly hydrophilic outer shell composed of a hydrosoluble co-polymer (Eudragit L100-55). The outer shell is tightly linked to the core and bears carboxylic groups capable of adsorbing high amounts (antigen loading ability of up to 20%, w/w) of native basic proteins, mainly by electrostatic interactions, while preserving their activity. In the present study we have evaluated in mice the safety and immunogenicity of new vaccine formulations composed of these nano- and microspheres and the HIV-1 Tat protein. Vaccines were administered by different routes, including intramuscular, subcutaneous or intranasal and the results were compared to immunization with Tat alone or with Tat delivered with the alum adjuvant. The data demonstrate that the nano- and microspheres/Tat formulations are safe and induce robust and long-lasting cellular and humoral responses in mice after systemic and/or mucosal immunization. These delivery systems may have great potential for novel Tat protein-based vaccines against HIV-1 and hold promise for other protein-based vaccines.
authors.affiliation: Department of Histology, University of Padova, Via A. Gabelli 63, 35122 Padova, Italy. antonella.caputo@unipd.it
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
authors.forename: Arianna
authors.initials: A
authors.lastname: Castaldello
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.forename: Rebecca
authors.initials: R
authors.lastname: Voltan
authors.forename: Francesca
authors.initials: F
authors.lastname: Bortolazzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Altavilla
authors.forename: Katia
authors.initials: K
authors.lastname: Sparnacci
authors.forename: Michele
authors.initials: M
authors.lastname: Laus
authors.forename: Luisa
authors.initials: L
authors.lastname: Tondelli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gavioli
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D018928:Immunity, Mucosal; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D054118:Nanospheres / Q000008:administration & dosage*
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; C421254:human immunodeficiency virus type 1 Tat vaccine; D015847:Interleukin-4; D007371:Interferon-gamma