Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention

被引:283
|
作者
Goncalvez, Ana P. [1 ]
Engle, Ronald E.
St. Claire, Marisa
Purcell, Robert H.
Lai, Ching-Juh
机构
[1] NIAID, Mol Viral Biol Sect, NIH, Rockville, MD 20850 USA
[2] NIAID, Hepatitis Viruses Sect, NIH, Rockville, MD 20850 USA
[3] Bioqual Inc, Rockville, MD 20850 USA
关键词
antibody-dependent enhancement; nonhuman primate model; Fc mutations; cross-reactive mAb;
D O I
10.1073/pnas.0703498104
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
Infection with dengue virus (DENV) or any other flavivirus induces cross-reactive, but weakly neutralizing or nonneutralizing, antibodies that recognize epitopes involving the fusion peptide in the envelope glycoprotein. Humanized mAb IgG 1A5, derived from a chimpanzee, shares properties of cross-reactive antibodies. mAb IgG 1A5 up-regulated DENV infection by a mechanism of antibody-dependent enhancement (ADE) in a variety of Fc receptor-bearing cells in vitro. A 10- to 1,000-fold increase of viral yield in K562 cells, dependent on the DENV serotype, was observed over a range of subneutralizing concentrations of IgG 1A5. A significant increase of DENV-4 viremia titers (up to 100-fold) was also demonstrated in juvenile rhesus monkeys immunized with passively transferred dilutions of IgG 1A5. These results, together with earlier findings of AIDE of DENV-2 infection by a polyclonal serum, establish the primate model for analysis of ADE. Considering the abundance of these cross-reactive antibodies, our observations confirm that significant viral amplification could occur during DENV infections in humans with prior infection or with maternally transferred immunity, possibly leading to severe dengue. Strategies to eliminate ADE were explored by altering the antibody Fc structures responsible for binding to Fc receptors. IgG 1A5 variants, containing amino acid substitutions from the Fc region of IgG2 or IgG4 antibodies, reduced but did not eliminate DENV-4-enhancing activity in K562 cells. Importantly, a 9-aa deletion at the N terminus of the CH2 domain in the Fc region abrogated the enhancing activity.
引用
收藏
页码:9422 / 9427
页数:6
相关论文
共 50 条
  • [1] ANTIBODY DETERMINANTS OF PROTECTION AND ENHANCEMENT OF SECONDARY DENGUE VIRUS INFECTION IN VITRO AND IN VIVO
    Williams, Katherine L.
    Lachica, Ruben
    Flores, Diana
    Wahala, Wahala
    de Silva, Aravinda M.
    Beltramello, Martina
    Sallusto, Federica
    Lanzavecchia, Antonio
    Beatty, P. Robert
    Harris, Eva
    [J]. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2009, 81 (05): : 121 - 121
  • [2] ANTIBODY-MEDIATED ENHANCEMENT OF RESPIRATORY SYNCYTIAL VIRUS-INFECTION
    GIMENEZ, B
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1990, 162 (05): : 1211 - 1211
  • [3] ANTIBODY-MEDIATED ENHANCEMENT OF RABIES VIRUS
    PORTERFIELD, JS
    [J]. NATURE, 1981, 290 (5807) : 542 - 542
  • [4] ANTIBODY-MEDIATED ENHANCEMENT OF INFECTION BY DENGUE VIRUS OF THE P815 MURINE MASTOCYTOMA CELL-LINE
    LEGRAND, LFS
    HOTTA, H
    HOTTA, S
    HOMMA, M
    [J]. BIKEN JOURNAL, 1986, 29 (02) : 51 - 55
  • [5] Substitution of the precursor peptide prevents anti-prM antibody-mediated antibody-dependent enhancement of dengue virus infection
    Wang, Ying
    Si, Lu-Lu
    Guo, Xiao-Lan
    Cui, Guo-hui
    Fang, Dan-Yun
    Zhou, Jun-Mei
    Yan, Hui-Jun
    Jiang, Li-Fang
    [J]. VIRUS RESEARCH, 2017, 229 : 57 - 64
  • [6] Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity
    Lum, Fok-Moon
    Couderc, Therese
    Chia, Bing-Shao
    Ong, Ruo-Yan
    Her, Zhisheng
    Chow, Angela
    Leo, Yee-Sin
    Kam, Yiu-Wing
    Renia, Laurent
    Lecuit, Marc
    Ng, Lisa F. P.
    [J]. SCIENTIFIC REPORTS, 2018, 8
  • [7] The stoichiometry of antibody-mediated neutralization and enhancement of west nile virus infection
    Pierson, Theodore C.
    Xu, Qing
    Nelson, Steevenson
    Oliphant, Theodore
    Nybakken, Grant E.
    Fremont, Daved H.
    Diamond, Michael S.
    [J]. CELL HOST & MICROBE, 2007, 1 (02) : 135 - 145
  • [8] Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity
    Fok-Moon Lum
    Thérèse Couderc
    Bing-Shao Chia
    Ruo-Yan Ong
    Zhisheng Her
    Angela Chow
    Yee-Sin Leo
    Yiu-Wing Kam
    Laurent Rénia
    Marc Lecuit
    Lisa F. P. Ng
    [J]. Scientific Reports, 8
  • [9] PREVENTION OF HCV INFECTION IN CHIMPANZEES FOLLOWING ANTIBODY-MEDIATED IN-VITRO NEUTRALIZATION
    FARCI, P
    ALTER, HJ
    WONG, D
    SHAPIRO, M
    PURCELL, RH
    [J]. HEPATOLOGY, 1993, 18 (04) : A111 - A111
  • [10] PREVENTION OF HEPATITIS-C VIRUS-INFECTION IN CHIMPANZEES AFTER ANTIBODY-MEDIATED IN-VITRO NEUTRALIZATION
    FARCI, P
    ALTER, HJ
    WONG, DC
    MILLER, RH
    GOVINDARAJAN, S
    ENGLE, R
    SHAPIRO, M
    PURCELL, RH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) : 7792 - 7796