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

被引：153

作者：

Bagnoli, Fabio ^{[1
]}

Fontana, Maria Rita ^{[1
]}

Soldaini, Elisabetta ^{[1
]}

Mishra, Ravi P. N. ^{[1
]}

Fiaschi, Luigi ^{[1
]}

Cartocci, Elena ^{[1
]}

Nardi-Dei, Vincenzo ^{[1
]}

Ruggiero, Paolo ^{[1
]}

Nosari, Sarah ^{[1
]}

De Falco, Maria Grazia ^{[1
]}

Lofano, Giuseppe ^{[1
]}

Marchi, Sara ^{[1
]}

Galletti, Bruno ^{[1
]}

Mariotti, Paolo ^{[1
]}

Bacconi, Marta ^{[1
]}

Torre, Antonina ^{[1
]}

Maccari, Silvia ^{[1
]}

Scarselli, Maria ^{[1
]}

Rinaudo, C. Daniela ^{[1
]}

Inoshima, Naoko ^{[2
]}

Savino, Silvana ^{[1
]}

Mori, Elena ^{[1
]}

Rossi-Paccani, Silvia ^{[1
]}

Baudner, Barbara ^{[1
]}

Pallaoro, Michele ^{[1
]}

Swennen, Erwin ^{[1
]}

Petracca, Roberto ^{[1
]}

Brettoni, Cecilia ^{[1
]}

Liberatori, Sabrina ^{[1
]}

Norais, Nathalie ^{[1
]}

Monaci, Elisabetta ^{[1
]}

Wardenburg, Juliane Bubeck ^{[2
]}

Schneewind, Olaf ^{[3
]}

O'Hagan, Derek T. ^{[1
]}

Valiante, Nicholas M. ^{[1
]}

Bensi, Giuliano ^{[1
]}

Bertholet, Sylvie ^{[1
]}

De Gregorio, Ennio ^{[1
]}

Rappuoli, Rino ^{[1
]}

Grandi, Guido ^{[1
]}

机构：

[1] Novartis Vaccines Res Ctr, I-53100 Siena, Italy

[2] Univ Chicago, Dept Pediat & Microbiol, Chicago, IL 60637 USA

[3] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2015年 / 112卷 / 12期

关键词：

Staphylococcus aureus; vaccine; TLR7; adjuvant; Hla; ALPHA-HEMOLYSIN; INFECTIONS; FHUD2; MICE; IDENTIFICATION; IMMUNITY; CELLS; MODEL;

D O I：

10.1073/pnas.1424924112

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Both active and passive immunization strategies against Staphylococcus aureus have thus far failed to show efficacy in humans. With the attempt to develop an effective S. aureus vaccine, we selected five conserved antigens known to have different roles in S. aureus pathogenesis. They include the secreted factors a-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 relevant S. aureus strains. 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 against S. aureus.

引用

页码：3680 / 3685

页数：6

共 23 条

[1] Inferring reasons for the failure of Staphylococcus aureus vaccines in clinical trials [J].