Induction of humoral and enhanced cellular immune responses by novel core-shell nanosphere- and microsphere-based vaccine formulations following systemic and mucosal administration.
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.
Caputo
Antonella
A
Department of Histology, University of Padova, Via A. Gabelli 63, 35122 Padova, Italy. antonella.caputo@unipd.it
Castaldello
Arianna
A
Brocca-Cofano
Egidio
E
Voltan
Rebecca
R
Bortolazzi
Francesca
F
Altavilla
Giuseppe
G
Sparnacci
Katia
K
Laus
Michele
M
Tondelli
Luisa
L
Gavioli
Riccardo
R
Ensoli
Barbara
B
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*
D016915:AIDS Vaccines; D015483:HIV Antibodies; C421254:human immunodeficiency virus type 1 Tat vaccine; D015847:Interleukin-4; D007371:Interferon-gamma