Universal vaccine against influenza virus: linking TLR signaling to anti-viral protection.

作者: Nicole Schmitz , Roger R. Beerli , Monika Bauer , Andrea Jegerlehner , Klaus Dietmeier

DOI: 10.1002/EJI.201041225

关键词:

摘要: A vaccine protecting against all influenza strains is a long-sought goal, particularly for emerging pandemics. As previously shown, vaccines based on the highly conserved extracellular domain of M2 (M2e) may protect strains. Here, we demonstrate that M2e-specific monoclonal antibodies (mAbs) mice from lethal infection. To be protective, had to able bind Fc receptors and fix complement. Furthermore, mAbs IgG2c isotype were protective in mice, while identical specificity, but IgG1 isotype, failed prevent disease. These findings readily translated into design. targeting absence toll-like receptor (TLR) 7 ligand primarily induced IgG1, whilst same linked TLR7 yielded high levels antibodies. Although both protected challenge, treated with containing showed significantly lower morbidity. In accordance these findings, vaccination TLR7(-/-) did not result protection challenge. Hence, innate immune system required direct switching toward more IgG2a/c

参考文章(40)
W. Gerhard, K. Mozdzanowska, G. Palladino, Shaohong Liang, Heterosubtypic immunity to influenza type A virus in mice. Effector mechanisms and their longevity. Journal of Immunology. ,vol. 152, pp. 1653- 1661 ,(1994)
Monika Bauer, Nicole Schmitz, Regula B Buser, Myriam Gwerder, Simone Muntwiler, Wolfgang A Renner, Philippe Saudan, Martin F Bachmann, Roger R Beerli, Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against Influenza A M2 protein Virology Journal. ,vol. 6, pp. 224- 224 ,(2009) , 10.1186/1743-422X-6-224
Felix Geeraedts, Nadege Goutagny, Veit Hornung, Martina Severa, Aalzen de Haan, Judith Pool, Jan Wilschut, Katherine A. Fitzgerald, Anke Huckriede, Superior Immunogenicity of Inactivated Whole Virus H5N1 Influenza Vaccine is Primarily Controlled by Toll-like Receptor Signalling PLoS Pathogens. ,vol. 4, pp. e1000138- ,(2008) , 10.1371/JOURNAL.PPAT.1000138
Laurel Yong-Hwa Lee, Do Lien Anh Ha, Cameron Simmons, Menno D. de Jong, Nguyen Van Vinh Chau, Reto Schumacher, Yan Chun Peng, Andrew J. McMichael, Jeremy J. Farrar, Geoffrey L. Smith, Alain R.M. Townsend, Brigitte A. Askonas, Sarah Rowland-Jones, Tao Dong, Erratum: Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals (Journal of Clinical Investigation (2008) 118, 10, (3478-3490) doi:10.1172/JCI32460) Journal of Clinical Investigation. ,vol. 122, pp. 4301- ,(2012) , 10.1172/JCI66865
B. Schwartz, P. Wortley, Mass Vaccination for Annual and Pandemic Influenza Current Topics in Microbiology and Immunology. ,vol. 304, pp. 131- 152 ,(2006) , 10.1007/3-540-36583-4_8
Falk Nimmerjahn, Jeffrey V. Ravetch, Fc-receptors as regulators of immunity. Advances in Immunology. ,vol. 96, pp. 179- 204 ,(2007) , 10.1016/S0065-2776(07)96005-8
Andrea Jegerlehner, Patrik Maurer, Juliana Bessa, Heather J. Hinton, Manfred Kopf, Martin F. Bachmann, TLR9 signaling in B cells determines class switch recombination to IgG2a. Journal of Immunology. ,vol. 178, pp. 2415- 2420 ,(2007) , 10.4049/JIMMUNOL.178.4.2415
Sabine Neirynck, Tom Deroo, Xavier Saelens, Peter Vanlandschoot, Willy Min Jou, Walter Fiers, A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nature Medicine. ,vol. 5, pp. 1157- 1163 ,(1999) , 10.1038/13484