MF59-and Al(OH)3-adjuvanted Staphylococcus aureus (4C-staph) vaccines induce sustained protective humoral and cellular immune responses, with a critical role for effector CD4 T cells at low antibody titers

被引:19
作者
Monaci, Elisabetta [1 ]
Mancini, Francesca [1 ,2 ]
Lofano, Giuseppe [1 ,3 ]
Bacconi, Marta [1 ,4 ]
Tavarini, Simona [1 ]
Sammicheli, Chiara [1 ]
Arcidiacono, Letizia [1 ]
Giraldi, Monica [1 ]
Galletti, Bruno [1 ]
Paccani, Silvia Rossi [1 ]
Torre, Antonina [1 ]
Fontana, Maria Rita [1 ]
Grandi, Guido [1 ]
de Gregorio, Ennio [1 ]
Bensi, Giuliano [1 ]
Chiarot, Emiliano [1 ]
Nuti, Sandra [1 ]
Bagnoli, Fabio [1 ]
Soldaini, Elisabetta [1 ]
Bertholet, Sylvie [1 ]
机构
[1] Novartis Vaccines & Diagnost SRL, Res Ctr, I-53100 Siena, Italy
[2] Univ Padua, Dept Biomed Sci, Padua, Italy
[3] Univ Roma La Sapienza, Dept Biol & Biotechnol Charles Darwin, I-00185 Rome, Italy
[4] Univ Siena, Dept Biotechnol Chem & Pharm, I-53100 Siena, Italy
来源
FRONTIERS IN IMMUNOLOGY | 2015年 / 6卷
关键词
Staphylococcus aureus; bacterial infection; vaccination; adjuvant; antibodies; T cells; mice; MURINE MODEL; PASSIVE-IMMUNIZATION; BACTERIAL-INFECTION; ALPHA-HEMOLYSIN; SKIN INFECTION; MOUSE MODEL; FHUD2; HYPOGAMMAGLOBULINEMIA; INTERLEUKIN-17A; IDENTIFICATION;
D O I
10.3389/fimmu.2015.00439
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Staphylococcus aureus (S. aureus) is an important opportunistic pathogen that may cause invasive life-threatening infections, like sepsis and pneumonia. Due to the increasing antibiotic resistance, the development of an effective vaccine against S. aureus is needed. Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity. In this study, we show that adjuvanting a multivalent vaccine (4C-Staph) with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T-cell responses compared to alum and conferred protection in the peritonitis model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T-cell responses, and protected mice from infection up to 4 months after immunization. Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted mice or B cell-deficient mice, we demonstrated that both T and B-cell responses contributed to 4C-Staph vaccine-mediated protective immunity. However, the role of CD4 T cells seemed more evident in the presence of low-antibody responses. This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S. aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen.
引用
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页码:1 / 11
页数:11
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