Details

Autor(en) / Beteiligte

• Bagnoli, Fabio
• Fontana, Maria Rita
• Soldaini, Elisabetta
• Mishra, Ravi P. N.
• Fiaschi, Luigi
• Cartocci, Elena
• Nardi-Dei, Vincenzo
• Ruggiero, Paolo
• Nosari, Sarah
• De Falco, Maria Grazia
• Lofano, Giuseppe
• Marchi, Sara
• Galletti, Bruno
• Mariotti, Paolo
• Bacconi, Marta
• Torre, Antonina
• Maccari, Silvia
• Scarselli, Maria
• Rinaudo, C. Daniela
• Inoshima, Naoko
• Savino, Silvana
• Mori, Elena
• Rossi-Paccani, Silvia
• Baudner, Barbara
• Pallaoro, Michele
• Swennen, Erwin
• Petracca, Roberto
• Brettoni, Cecilia
• Liberatori, Sabrina
• Norais, Nathalie
• Monaci, Elisabetta
• Wardenburg, Juliane Bubeck
• Schneewind, Olaf
• O’Hagan, Derek T.
• Valiante, Nicholas M.
• Bensi, Giuliano
• Bertholet, Sylvie
• DeGregorio, Ennio
• Rappuoli, Rino
• Grandi, Guido

Titel

Vaccine composition formulated with a novel TLR7-dependent adjuvant induces high and broad protection againstStaphylococcus aureus

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-03, Vol.112 (12), p.3680-3685

Ort / Verlag

National Academy of Sciences

Erscheinungsjahr

2015

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Both active and passive immunization strategies againstStaphylococcus aureushave thus far failed to show efficacy in humans. With the attempt to develop an effectiveS. aureusvaccine, we selected five conserved antigens known to have different roles inS. aureuspathogenesis. They include the secreted factors α-hemolysin (Hla), ess extracellular A (EsxA), and ess extracellular B (EsxB) and the two surface proteins ferric hydroxamate uptake D2 and conserved staphylococcal antigen 1A. The combined vaccine antigens formulated with aluminum hydroxide induced antibodies with opsonophagocytic and functional activities and provided consistent protection in four mouse modelswhen challengedwith a panel of epidemiologically relevantS. aureusstrains. The importance of antibodies in protection was demonstrated by passive transfer experiments. Furthermore, when formulated with a toll-like receptor 7-dependent (TLR7) agonist recently designed and developed in our laboratories (SMIP.7–10) adsorbed to alum, the five antigens provided close to 100% protection against four different staphylococcal strains. The new formulation induced not only high antibody titers but also a Th1 skewed immune response as judged by antibody isotype and cytokine profiles. In addition, low frequencies of IL-17–secreting T cells were also observed. Altogether, our data demonstrate that the rational selection of mixtures of conserved antigens combined with Th1/Th17 adjuvants can lead to promising vaccine formulations againstS. aureus.