Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors

被引:319
作者
Yu, Xiaocong [1 ,2 ]
Tsibane, Tshidi [3 ]
McGraw, Patricia A. [1 ,2 ]
House, Frances S. [1 ,2 ]
Keefer, Christopher J. [1 ,2 ]
Hicar, Mark D. [1 ,2 ]
Tumpey, Terrence M. [4 ]
Pappas, Claudia [3 ,4 ]
Perrone, Lucy A. [4 ]
Martinez, Osvaldo [3 ]
Stevens, James [4 ,5 ,6 ]
Wilson, Ian A. [5 ,6 ]
Aguilar, Patricia V. [3 ]
Altschuler, Eric L. [7 ]
Basler, Christopher F. [3 ]
Crowe, James E., Jr. [1 ,2 ]
机构
[1] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA
[3] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
[4] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA
[5] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[6] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[7] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature07231
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era(1). Recent work has recovered the gene sequences of this unusual strain(2), so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes(3,4). However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin ( HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross- reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross- react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus- neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus- neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure - well into the tenth decade of life.
引用
收藏
页码:532 / U41
页数:6
相关论文
共 30 条
[1]   Duration of humoral immunity to common viral and vaccine antigens [J].
Amanna, Ian J. ;
Carlson, Nichole E. ;
Slifka, Mark K. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (19) :1903-1915
[2]   Immunity and immunological memory following smallpox vaccination [J].
Amanna, Ian J. ;
Slifka, Mark K. ;
Crotty, Shane .
IMMUNOLOGICAL REVIEWS, 2006, 211 :320-337
[3]   Maintenance of serological memory by polyclonal activation of human memory B cells [J].
Bernasconi, NL ;
Traggiai, E ;
Lanzavecchia, A .
SCIENCE, 2002, 298 (5601) :2199-2202
[4]   The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin [J].
Brownlee, GG ;
Fodor, E .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES, 2001, 356 (1416) :1871-1876
[5]   THE ANTIGENIC STRUCTURE OF THE INFLUENZA-VIRUS A/PR/8/34 HEMAGGLUTININ (H-1 SUBTYPE) [J].
CATON, AJ ;
BROWNLEE, GG ;
YEWDELL, JW ;
GERHARD, W .
CELL, 1982, 31 (02) :417-427
[6]   Influenza virus hemagglutinin and neuraminidase, but not the matrix protein, are required for assembly and budding of plasmid-derived virus-like particles [J].
Chen, Benjamin J. ;
Leser, George P. ;
Morita, Eiji ;
Lamb, Robert A. .
JOURNAL OF VIROLOGY, 2007, 81 (13) :7111-7123
[7]   Cutting edge: Long-term B cell memory in humans after smallpox vaccination [J].
Crotty, S ;
Felgner, P ;
Davies, H ;
Glidewell, J ;
Villarreal, L ;
Ahmed, R .
JOURNAL OF IMMUNOLOGY, 2003, 171 (10) :4969-4973
[8]   A single amino acid substitution in 1918 influenza virus hemagglutinin changes receptor binding specificity [J].
Glaser, L ;
Stevens, J ;
Zamarin, D ;
Wilson, IA ;
García-Sastre, A ;
Tumpey, TM ;
Basler, CF ;
Taubenberger, JK ;
Palese, P .
JOURNAL OF VIROLOGY, 2005, 79 (17) :11533-11536
[9]   Duration of antiviral immunity after smallpox vaccination [J].
Hammarlund, E ;
Lewis, MW ;
Hansen, SG ;
Strelow, LI ;
Nelson, JA ;
Sexton, GJ ;
Hanifin, JM ;
Slifka, MK .
NATURE MEDICINE, 2003, 9 (09) :1131-1137
[10]   Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic [J].
Johnson, NPAS ;
Mueller, J .
BULLETIN OF THE HISTORY OF MEDICINE, 2002, 76 (01) :105-115