Broadly neutralizing anti-IAV antibodies

A broadly neutralizing anti-IAV antibody is a neutralizing antibody that is effective against several strains of the influenza A virus (IAV).

properties

Neutralizing antibodies against influenza viruses are, for example, the antibodies CR6261 , C179 , FI6 and MAb 3.1 , which all bind to the stem region in the hemagglutinin . There are 18 serotypes of the influenza A virus, H1 through H18.

In 2011, FI6 was described that binds to at least 16 serotypes of hemagglutinin and inhibits their function. Analogous to the broadly neutralizing anti-HIV antibodies that have been known for some time , a search was made for neutralizing antibodies effective against several strains of the influenza A virus. FI6 binds to conserved areas in the hemagglutinin (stem region), which are also examined in the course of the vaccine development of influenza vaccines . In 2012, CR9114 was described, which binds to influenza viruses of types A (H1 – H5, H7 and H9, H10, H12, H13, H15 and H16) and has a neutralizing effect on H1 – H12 and H14 as well as influenza B viruses.

Applications

FI6 is being studied for passive immunization by infusing the antibody. Furthermore, the DNA of FI6 is used for transient gene therapy with AAV vectors in the sense of a therapeutic vaccine in order to achieve the formation of FI6 in the nasal and pharyngeal mucosa.

literature

NS Laursen, IA Wilson: Broadly neutralizing antibodies against influenza viruses. In: Antiviral research. Volume 98, number 3, June 2013, pp. 476-483, doi : 10.1016 / j.antiviral.2013.03.021 , PMID 23583287 , PMC 3987986 (free full text).

Individual evidence

^ Y. Lu, JP Welsh, JR Swartz: Production and stabilization of the trimeric influenza hemagglutinin stem domain for potentially broadly protective influenza vaccines. In: Proceedings of the National Academy of Sciences . Volume 111, number 1, January 2014, pp. 125–130, doi : 10.1073 / pnas.1308701110 , PMID 24344259 , PMC 3890838 (free full text).
↑ A. Wyrzucki, C. Dreyfus, I. Kohler, M. Steck, IA Wilson, L. Hangartner: Alternative recognition of the conserved stem epitope in influenza A virus hemagglutinin by a VH3-30-encoded heterosubtypic antibody. In: Journal of virology. Volume 88, number 12, June 2014, pp. 7083-7092, doi : 10.1128 / JVI.00178-14 , PMID 24719426 , PMC 4054347 (free full text).
↑ S. Tong, X. Zhu, Y. Li, M. Shi, J. Zhang, M. Bourgeois, H. Yang, X. Chen, S. Recuenco, J. Gomez, LM Chen, A. Johnson, Y. Tao, C. Dreyfus, W. Yu, R. McBride, PJ Carney, AT Gilbert, J. Chang, Z. Guo, CT Davis, JC Paulson, J. Stevens, CE Rupprecht, EC Holmes, IA Wilson, RO Donis: New world bats harbor various influenza A viruses. In: PLoS pathogens. Volume 9, number 10, 2013, p. E1003657, doi : 10.1371 / journal.ppat.1003657 , PMID 24130481 , PMC 3794996 (free full text).
^ ^A ^b D. Corti, J. Voss, SJ Gamblin, G. Codoni, A. Macagno, D. Jarrossay, SG Vachieri, D. Pinna, A. Minola, F. Vanzetta, C. Silacci, BM Fernandez-Rodriguez, G. Agatic, S. Bianchi, I. Giacchetto-Sasselli, L. Calder, F. Sallusto, P. Collins, LF Haire, N. Temperton, JP Langedijk, JJ Skehel, A. Lanzavecchia: A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. In: Science. Volume 333, Number 6044, August 2011, pp. 850-856, doi : 10.1126 / science.1205669 , PMID 21798894 .
↑ C. Dreyfus, NS Laursen, T. Kwaks, D. Zuijdgeest, R. Khayat, DC Ekiert, JH Lee, Z. Metlagel, MV Bujny, M. Jongeneelen, R. van der Vlugt, M. Lamrani, HJ Korse, E. Geelen, .. Sahin, M. Sieuwerts, JP Brakenhoff, R. Vogels, OT Li, LL Poon, M. Peiris, W. Koudstaal, AB Ward, IA Wilson, J. Goudsmit, RH Fri: Highly conserved protective epitopes on influenza B viruses. In: Science. Volume 337, number 6100, September 2012, pp. 1343-1348, doi : 10.1126 / science.1222908 , PMID 22878502 , PMC 3538841 (free full text).
↑ MP Limberis, VS Adam, G. Wong, J. Gren, D. Kobasa, TM Ross, GP Kobinger, A. Tretiakova, JM Wilson: Intranasal antibody gene transfer in mice and ferrets elicits broad protection against pandemic influenza. In: Science Translational Medicine . Volume 5, number 187, May 2013, p. 187ra72, doi : 10.1126 / scitranslmed.3006299 , PMID 23720583 , PMC 4596530 (free full text).

[1] Y. Lu, JP Welsh, JR Swartz: Production and stabilization of the trimeric influenza hemagglutinin stem domain for potentially broadly protective influenza vaccines. In: Proceedings of the National Academy of Sciences . Volume 111, number 1, January 2014, pp. 125–130, doi : 10.1073 / pnas.1308701110 , PMID 24344259 , PMC 3890838 (free full text).

[2] A. Wyrzucki, C. Dreyfus, I. Kohler, M. Steck, IA Wilson, L. Hangartner: Alternative recognition of the conserved stem epitope in influenza A virus hemagglutinin by a VH3-30-encoded heterosubtypic antibody. In: Journal of virology. Volume 88, number 12, June 2014, pp. 7083-7092, doi : 10.1128 / JVI.00178-14 , PMID 24719426 , PMC 4054347 (free full text).

[3] S. Tong, X. Zhu, Y. Li, M. Shi, J. Zhang, M. Bourgeois, H. Yang, X. Chen, S. Recuenco, J. Gomez, LM Chen, A. Johnson, Y. Tao, C. Dreyfus, W. Yu, R. McBride, PJ Carney, AT Gilbert, J. Chang, Z. Guo, CT Davis, JC Paulson, J. Stevens, CE Rupprecht, EC Holmes, IA Wilson, RO Donis: New world bats harbor various influenza A viruses. In: PLoS pathogens. Volume 9, number 10, 2013, p. E1003657, doi : 10.1371 / journal.ppat.1003657 , PMID 24130481 , PMC 3794996 (free full text).

[Corti-4] A ^b D. Corti, J. Voss, SJ Gamblin, G. Codoni, A. Macagno, D. Jarrossay, SG Vachieri, D. Pinna, A. Minola, F. Vanzetta, C. Silacci, BM Fernandez-Rodriguez, G. Agatic, S. Bianchi, I. Giacchetto-Sasselli, L. Calder, F. Sallusto, P. Collins, LF Haire, N. Temperton, JP Langedijk, JJ Skehel, A. Lanzavecchia: A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. In: Science. Volume 333, Number 6044, August 2011, pp. 850-856, doi : 10.1126 / science.1205669 , PMID 21798894 .

[5] C. Dreyfus, NS Laursen, T. Kwaks, D. Zuijdgeest, R. Khayat, DC Ekiert, JH Lee, Z. Metlagel, MV Bujny, M. Jongeneelen, R. van der Vlugt, M. Lamrani, HJ Korse, E. Geelen, .. Sahin, M. Sieuwerts, JP Brakenhoff, R. Vogels, OT Li, LL Poon, M. Peiris, W. Koudstaal, AB Ward, IA Wilson, J. Goudsmit, RH Fri: Highly conserved protective epitopes on influenza B viruses. In: Science. Volume 337, number 6100, September 2012, pp. 1343-1348, doi : 10.1126 / science.1222908 , PMID 22878502 , PMC 3538841 (free full text).

[6] MP Limberis, VS Adam, G. Wong, J. Gren, D. Kobasa, TM Ross, GP Kobinger, A. Tretiakova, JM Wilson: Intranasal antibody gene transfer in mice and ferrets elicits broad protection against pandemic influenza. In: Science Translational Medicine . Volume 5, number 187, May 2013, p. 187ra72, doi : 10.1126 / scitranslmed.3006299 , PMID 23720583 , PMC 4596530 (free full text).