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

Proceedings of the National Academy of Sciences of the United States of America
Fabio BagnoliGuido Grandi

Abstract

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 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 models when challenged with 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 cyto...Continue Reading

References

Apr 21, 2004·Immunology·Terri N Ellis, Blaine L Beaman
Jan 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Monica L BurtsDominique M Missiakas
Dec 3, 2005·Nature Reviews. Microbiology·Timothy J Foster
May 26, 2006·Nature Reviews. Immunology·Gregg J Silverman, Carl S Goodyear
Apr 17, 2007·Current Opinion in Immunology·Brigitta Stockinger, Marc Veldhoen
Feb 13, 2008·The Journal of Experimental Medicine·Juliane Bubeck Wardenburg, Olaf Schneewind
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Georgia A Wilke, Juliane Bubeck Wardenburg
Aug 18, 2010·The Journal of Experimental Medicine·Hwan Keun KimOlaf Schneewind
Jul 2, 2011·Nature Reviews. Immunology·Lloyd S Miller, John S Cho
Feb 23, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Richard A Proctor
Aug 25, 2012·Frontiers in Cellular and Infection Microbiology·Fabio BagnoliGuido Grandi
Apr 4, 2013·JAMA : the Journal of the American Medical Association·Vance G FowlerAjoke Sobanjo-ter Meulen
Dec 18, 2013·Nature Reviews. Microbiology·Timothy J FosterMagnus Höök
Nov 21, 2014·Science Translational Medicine·Tom Y-H WuNicholas M Valiante

❮ Previous
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Citations

Jun 13, 2015·International Journal of Molecular Sciences·Enrico MalitoMatthew J Bottomley
Mar 1, 2016·Frontiers in Microbiology·Shahper N Khan, Asad U Khan
Jan 1, 2016·Trends in Pharmacological Sciences·William E SauseVictor J Torres
Sep 8, 2015·Current Opinion in Microbiology·Ingrid L ScullyAnnaliesa S Anderson
Jul 21, 2015·Bioconjugate Chemistry·Hiroyuki ShinchiDennis A Carson
Sep 30, 2016·Frontiers in Microbiology·Shideh V ShahmirzadiFriedrich Götz
Aug 16, 2016·Proteomics. Clinical Applications·Sebastian StentzelBarbara M Bröker
Jan 10, 2018·Frontiers in Microbiology·Skyla A DuncanVida A Dennis
Aug 12, 2016·Microbiology and Molecular Biology Reviews : MMBR·Minh Thu Nguyen, Friedrich Götz
Dec 24, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fiamma SalernoMonika C Wolkers
Sep 2, 2016·Nature Reviews. Disease Primers·Thomas L HollandVance G Fowler
Aug 17, 2019·Journal of Medical Microbiology·Abigail L CoughtrieStuart C Clarke
Apr 25, 2019·PLoS Biology·Salvatore RaieliVassili Soumelis
Apr 27, 2018·Critical Care : the Official Journal of the Critical Care Forum·Jared A GreenbergPhilip A Verhoef
Nov 5, 2015·Expert Opinion on Investigational Drugs·Cuong VuongMichael Otto
Nov 26, 2015·International Reviews of Immunology·Enrico D'AmelioRaffaele D'Amelio
Dec 22, 2015·Applied Microbiology and Biotechnology·Marta BacconiGiuliano Bensi
Jan 12, 2016·Human Vaccines & Immunotherapeutics·Alberto GrandiGuido Grandi
Dec 31, 2015·Expert Review of Proteomics·Danilo DonnarummaNathalie Norais
Apr 24, 2016·Folia Microbiologica·Charlene Babra WaryahTrilochan Mukkur
May 6, 2016·The Biochemical Journal·Gisela von HovenMatthias Husmann
Apr 28, 2016·Expert Review of Vaccines·Gustavo H DayanAnnaliesa S Anderson
Jun 16, 2016·Scientific Reports·Luigi SciettiSabrina Liberatori
Jan 26, 2017·The British Journal of Surgery·N MohamedA S Anderson
Mar 2, 2017·Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies·Allan DoctorKatri Typpo
Aug 9, 2017·Frontiers in Cellular and Infection Microbiology·Melania CrucianiEliana M Coccia

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