Cross-reacting antibodies enhance dengue virus infection in humans.
Dengue virus co-circulates as four serotypes, and sequential infections with more than one serotype are common. One hypothesis for the increased severity seen in secondary infections is antibody-dependent enhancement (ADE) leading to increased replication in Fc receptor-bearing cells. In this study, we have generated a panel of human monoclonal antibodies to dengue virus. Antibodies to the structural precursor-membrane protein (prM) form a major component of the response. These antibodies are highly cross-reactive among the dengue virus serotypes and, even at high concentrations, do not neutralize infection but potently promote ADE. We propose that the partial cleavage of prM from the viral surface reduces the density of antigen available for viral neutralization, leaving dengue viruses susceptible to ADE by antibody to prM, a finding that has implications for future vaccine design.
Dejnirattisai
Wanwisa
W
Department of Medicine, Imperial College London, London W12 0NN, UK.
Jumnainsong
Amonrat
A
Onsirisakul
Naruthai
N
Fitton
Patricia
P
Vasanawathana
Sirijitt
S
Limpitikul
Wannee
W
Puttikhunt
Chunya
C
Edwards
Carolyn
C
Duangchinda
Thaneeya
T
Supasa
Sunpetchuda
S
Chawansuntati
Kriangkrai
K
Malasit
Prida
P
Mongkolsapaya
Juthathip
J
Screaton
Gavin
G
D000330:Aedes; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement; D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology*; D053059:Dengue Vaccines / Q000276:immunology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology* / Q000502:physiology; D004664:Encephalitis Virus, Japanese / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D009000:Monocytes / Q000276:immunology / Q000821:virology; D011961:Receptors, Fc / Q000276:immunology; D012703:Serotyping; D020298:U937 Cells; D014759:Viral Envelope Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D053059:Dengue Vaccines; D011961:Receptors, Fc; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins
Nat Rev Microbiol. 2007 Jul;5(7):518-28
17558424
J Virol. 2008 Jul;82(13):6631-43
18448542
J Exp Med. 1977 Jul 1;146(1):201-17
406347
Am J Epidemiol. 1984 Nov;120(5):653-69
6496446
J Virol. 2008 Nov;82(21):10776-91
18715923
J Med Virol. 2008 Jan;80(1):125-33
18041028
Trans R Soc Trop Med Hyg. 1997 Sep-Oct;91(5):614-7
9463684
J Virol Methods. 2003 Apr;109(1):55-61
12668268
Science. 2008 Mar 28;319(5871):1834-7
18369148
Science. 2008 Mar 28;319(5871):1830-4
18369147
J Gen Virol. 1991 Jun;72 ( Pt 6):1323-9
1710648
Am J Epidemiol. 2000 Nov 1;152(9):793-9; discussion 804
11085389
Southeast Asian J Trop Med Public Health. 1996 Jun;27(2):228-36
9279982
J Gen Virol. 2008 Dec;89(Pt 12):3047-3051
19008392
J Immunol. 2008 Nov 1;181(9):5865-74
18941175
Immunol Rev. 2008 Oct;225:212-25
18837784
Nat Med. 2004 Aug;10(8):871-5
15247913
Am J Trop Med Hyg. 1989 Apr;40(4):418-27
2540664
J Immunol. 2006 Mar 1;176(5):2825-32
16493039
Nature. 2004 Jan 22;427(6972):313-9
14737159