The gp41 epitope, QARVLAVERY, is highly conserved and a potent inducer of IgA that neutralizes HIV-1 and inhibits viral transcytosis

作者: S Jain , K L Rosenthal

DOI: 10.1038/MI.2011.21

关键词: Conserved sequenceVirologyEpitopeGp41AntibodyImmunityMucosal immunologyImmunizationBiologyTranscytosisImmunology

摘要: Mucosal surfaces are the predominant site of human immunodeficiency virus (HIV)-1 transmission. For prophylactic approaches to effectively prevent HIV infection and subsequent dissemination, induction mucosally relevant protective immunity will be critical. Here, we have characterized antibody (Ab) response generated by a highly conserved gp41epitope, QARVLAVERY, in an optimized immunization model that elicits potent epitope-specific Abs serum, vaginal washes, fecal secretions immunized mice. Our results show QARVLAVERY is indeed inducer IgA importantly, QARVLAVERY-specific was effective neutralizing inhibiting viral transcytosis. Intriguingly, also approximate 1:1 ratio IgG:IgA serum mice, independent delivery regimen produced early systemic IgA, even before IgG. In light significantly high functionality inhibition transcytosis, attractive epitope considered mucosal vaccination strategies against HIV.

参考文章(111)
David C. Montefiori, Measuring HIV Neutralization in a Luciferase Reporter Gene Assay Methods in Molecular Biology. ,vol. 485, pp. 395- 405 ,(2009) , 10.1007/978-1-59745-170-3_26
Piconi S, Barassi C, Pastori C, Clerici M, Lopalco L, Longhi R, Siccardi Ag, Villa Ml, HIV neutralizing IgA in exposed seronegative subjects recognise an epitope within the gp41 coiled-coil pocket. Journal of Biological Regulators and Homeostatic Agents. ,vol. 14, pp. 15- 21 ,(2000)
Jan zur Megede, Derek O'Hagan, Padma Malyala, Amanda Goodsell, Michael Vajdy, Susan Barnett, Catherine Greer, Jina Kazzaz, Fengmin Zhou, John Polo, Manmohan Singh, Beta7-integrin independent enhancement of mucosal and systemic anti-HIV antibody responses following combined mucosal and systemic gene delivery Journal of Immunology. ,vol. 178, ,(2007)
Maaike Stoel, Han-Qing Jiang, Cleo C. van Diemen, Judy C. A. M. Bun, Peter M. Dammers, M. Christine Thurnheer, Frans G. M. Kroese, John J. Cebra, Nicolaas A. Bos, Restricted IgA Repertoire in Both B-1 and B-2 Cell-Derived Gut Plasmablasts Journal of Immunology. ,vol. 174, pp. 1046- 1054 ,(2005) , 10.4049/JIMMUNOL.174.2.1046
V. Raúl Gómez-Román, L. Jean Patterson, David Venzon, David Liewehr, Kris Aldrich, Ruth Florese, Marjorie Robert-Guroff, Vaccine-elicited antibodies mediate antibody-dependent cellular cytotoxicity correlated with significantly reduced acute viremia in rhesus macaques challenged with SIVmac251. Journal of Immunology. ,vol. 174, pp. 2185- 2189 ,(2005) , 10.4049/JIMMUNOL.174.4.2185
Claudia Devito, Kristina Broliden, Rupert Kaul, Lennart Svensson, Kari Johansen, Peter Kiama, Joshua Kimani, Lucia Lopalco, Stefania Piconi, Job J Bwayo, Francis Plummer, Mario Clerici, Jorma Hinkula, None, Mucosal and Plasma IgA from HIV-1-Exposed Uninfected Individuals Inhibit HIV-1 Transcytosis Across Human Epithelial Cells Journal of Immunology. ,vol. 165, pp. 5170- 5176 ,(2000) , 10.4049/JIMMUNOL.165.9.5170
Per Johan Klasse, Rüdiger Pipkorn, Jonas Blomberg, Kyou-Hoon Han, Bruce Hilton, James A. Ferretti, Three-dimensional structure and antigenicity of transmembrane-protein peptides of the human immunodeficiency virus type 1: Effects of a neutralization-escape substitution FEBS Letters. ,vol. 323, pp. 68- 72 ,(1993) , 10.1016/0014-5793(93)81450-E
Baojing Lu, Yi Huang, Li Huang, Bao Li, Zhenhua Zheng, Ze Chen, Jianjun Chen, Qinxue Hu, Hanzhong Wang, Effect of mucosal and systemic immunization with virus‐like particles of severe acute respiratory syndrome coronavirus in mice Immunology. ,vol. 130, pp. 254- 261 ,(2010) , 10.1111/J.1365-2567.2010.03231.X
T Lehner, L Tao, C Panagiotidi, L S Klavinskis, R Brookes, L Hussain, N Meyers, S E Adams, A J Gearing, L A Bergmeier, Mucosal model of genital immunization in male rhesus macaques with a recombinant simian immunodeficiency virus p27 antigen. Journal of Virology. ,vol. 68, pp. 1624- 1632 ,(1994) , 10.1128/JVI.68.3.1624-1632.1994
Juliana Bessa, Andrea Jegerlehner, Heather J. Hinton, Paul Pumpens, Philippe Saudan, Pascal Schneider, Martin F. Bachmann, Alveolar Macrophages and Lung Dendritic Cells Sense RNA and Drive Mucosal IgA Responses Journal of Immunology. ,vol. 183, pp. 3788- 3799 ,(2009) , 10.4049/JIMMUNOL.0804004