Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification

English version České info

Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate DV infection of myeloid cells in vitro by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody-dependent enhancement (ADE). However, despite decades of investigation, no in vivo model for antibody enhancement of dengue disease severity has been described. Analogous to human infants who receive anti-DV antibodies by transplacental transfer and develop severe dengue disease during primary infection, we show here that passive administration of anti-DV antibodies is sufficient to enhance DV infection and disease in mice using both mouse-adapted and clinical DV isolates. Antibody-enhanced lethal disease featured many of the hallmarks of severe dengue disease in humans, including thrombocytopenia, vascular leakage, elevated serum cytokine levels, and increased systemic viral burden in serum and tissue phagocytes. Passive transfer of a high dose of serotype-specific antibodies eliminated viremia, but lower doses of these antibodies or cross-reactive polyclonal or monoclonal antibodies all enhanced disease in vivo even when antibody levels were neutralizing in vitro. In contrast, a genetically engineered antibody variant (E60-N297Q) that cannot bind FcγR exhibited prophylactic and therapeutic efficacy against ADE-induced lethal challenge. These observations provide insight into the pathogenesis of antibody-enhanced dengue disease and identify a novel strategy for the design of therapeutic antibodies against dengue.

Vyšlo v časopise: Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification. PLoS Pathog 6(2): e32767. doi:10.1371/journal.ppat.1000790
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000790

Souhrn

Zdroje

1. RothmanAL

2004 Dengue: defining protective versus pathologic immunity. J Clin Invest 113 946 951

2. HalsteadSB

2007 Dengue. Lancet 370 1644 1652

3. WHO

1997 Dengue haemorrhagic fever: diagnosis, treatment, prevention, and control. Geneva World Health Organization

4. HalsteadSB

2003 Neutralization and antibody-dependent enhancement of dengue viruses. Adv Virus Res 60 421 467

5. KliksSC

NimmanityaS

NisalakA

BurkeDS

1988 Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 38 411 419

6. ChauTN

QuyenNT

ThuyTT

TuanNM

HoangDM

2008 Dengue in Vietnamese infants-results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity. J Infect Dis 198 516 524

7. HalsteadSB

1979 In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody. J Infect Dis 140 527 533

8. GoncalvezAP

EngleRE

St ClaireM

PurcellRH

LaiCJ

2007 Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. Proc Natl Acad Sci U S A 104 9422 9427

9. ShrestaS

ShararKL

PrigozhinDM

BeattyPR

HarrisE

2006 A murine model for dengue virus-induced lethal disease with increased vascular permeability. J Virol 80 10208 10217

10. KyleJL

BeattyPR

HarrisE

2007 Dengue virus infects macrophages and dendritic cells in a mouse model of infection. J Infect Dis 195 1808 1817

11. SchulW

LiuW

XuHY

FlamandM

VasudevanSG

2007 A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. J Infect Dis 195 665 674

12. BalsitisS

ColomaJ

CastroG

AlavaA

FloresD

2009 Tropism of dengue virus in mice and humans defined by viral nonstructural protein 3-specific immunostaining. Am J Trop Med Hyg 80 416 424

13. KyleJL

BalsitisS

ZhangL

BeattyPR

HarrisE

2008 Antibodies play a greater role than immune cells in heterologous protection against secondary dengue virus infection in a mouse model. Virology 380 296 303

14. KrausAA

MesserW

HaymoreLB

de SilvaAM

2007 Comparison of plaque- and flow cytometry-based methods for measuring dengue virus neutralization. J Clin Microbiol 45 3777 3780

15. FunaharaY

Sumarmo

ShirahataA

Setiabudy-DharmaR

1987 DHF characterized by acute type DIC with increased vascular permeability. Southeast Asian J Trop Med Public Health 18 346 350

16. NguyenTH

LeiHY

NguyenTL

LinYS

HuangKJ

2004 Dengue hemorrhagic fever in infants: a study of clinical and cytokine profiles. J Infect Dis 189 221 232

17. PerezAB

GarciaG

SierraB

AlvarezM

VazquezS

2004 IL-10 levels in Dengue patients: some findings from the exceptional epidemiological conditions in Cuba. J Med Virol 73 230 234

18. JessieK

FongMY

DeviS

LamSK

WongKT

2004 Localization of dengue virus in naturally infected human tissues, by immunohistochemistry and in situ hybridization. J Infect Dis 189 1411 1418

19. HumeDA

RobinsonAP

MacPhersonGG

GordonS

1983 The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Relationship between macrophages, Langerhans cells, reticular cells, and dendritic cells in lymphoid and hematopoietic organs. J Exp Med 158 1522 1536

20. HumeDA

PerryVH

GordonS

1984 The mononuclear phagocyte system of the mouse defined by immunohistochemical localisation of antigen F4/80: macrophages associated with epithelia. Anat Rec 210 503 512

21. PiersonTC

DiamondMS

2008 Molecular mechanisms of antibody-mediated neutralisation of flavivirus infection. Expert Rev Mol Med 10 e12

22. EndyTP

NisalakA

ChunsuttitwatS

VaughnDW

GreenS

2004 Relationship of preexisting dengue virus (DV) neutralizing antibody levels to viremia and severity of disease in a prospective cohort study of DV infection in Thailand. J Infect Dis 189 990 1000

23. BoonnakK

SlikeBM

BurgessTH

MasonRM

WuSJ

2008 Role of dendritic cells in antibody-dependent enhancement of dengue virus infection. J Virol 82 3939 3951

24. CrillWD

ChangGJ

2004 Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes. J Virol 78 13975 13986

25. OliphantT

NybakkenGE

EngleM

XuQ

NelsonCA

2006 Antibody recognition and neutralization determinants on domains I and II of West Nile Virus envelope protein. J Virol 80 12149 12159

26. OliphantT

EngleM

NybakkenGE

DoaneC

JohnsonS

2005 Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus. Nat Med 11 522 530

27. TaoMH

MorrisonSL

1989 Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. J Immunol 143 2595 2601

28. StavenhagenJB

GorlatovS

TuaillonN

RankinCT

LiH

2007 Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcgamma receptors. Cancer Res 67 8882 8890

29. AtrasheuskayaA

PetzelbauerP

FredekingTM

IgnatyevG

2003 Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection. FEMS Immunol Med Microbiol 35 33 42

30. ChenHC

HofmanFM

KungJT

LinYD

Wu-HsiehBA

2007 Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. J Virol 81 5518 5526

31. LinYL

LiaoCL

ChenLK

YehCT

LiuCI

1998 Study of Dengue virus infection in SCID mice engrafted with human K562 cells. J Virol 72 9729 9737

32. AnJ

Kimura-KurodaJ

HirabayashiY

YasuiK

1999 Development of a novel mouse model for dengue virus infection. Virology 263 70 77

33. BlaneyJEJr

JohnsonDH

ManiponGG

FirestoneCY

HansonCT

2002 Genetic basis of attenuation of dengue virus type 4 small plaque mutants with restricted replication in suckling mice and in SCID mice transplanted with human liver cells. Virology 300 125 139

34. WuSF

LiaoCL

LinYL

YehCT

ChenLK

2003 Evaluation of protective efficacy and immune mechanisms of using a non-structural protein NS1 in DNA vaccine against dengue 2 virus in mice. Vaccine 21 3919 3929

35. BenteDA

MelkusMW

GarciaJV

Rico-HesseR

2005 Dengue fever in humanized NOD/SCID mice. J Virol 79 13797 13799

36. KuruvillaJG

TroyerRM

DeviS

AkkinaR

2007 Dengue virus infection and immune response in humanized RAG2(−/−)gamma(c)(−/−) (RAG-hu) mice. Virology 369 143 152

37. HottaH

MurakamiI

MiyasakiK

TakedaY

ShiraneH

1981 Inoculation of dengue virus into nude mice. J Gen Virol 52 71 76

38. ShrestaS

KyleJL

SniderHM

BasavapatnaM

BeattyPR

2004 Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical. J Virol 78 2701 2710

39. CoudercT

ChretienF

SchilteC

DissonO

BrigitteM

2008 A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog 4 e29 doi:10.1371/journal.ppat.0040029

40. MeierKC

GardnerCL

KhoretonenkoMV

KlimstraWB

RymanKD

2009 A mouse model for studying viscerotropic disease caused by yellow fever virus infection. PLoS Pathog 5 e1000614 doi:10.1371/journal.ppat.1000614

41. WeissRC

ScottFW

1981 Antibody-mediated enhancement of disease in feline infectious peritonitis: comparisons with dengue hemorrhagic fever. Comp Immunol Microbiol Infect Dis 4 175 189

42. BarrettAD

GouldEA

1986 Antibody-mediated early death in vivo after infection with yellow fever virus. J Gen Virol 67 (Pt 11) 2539 2542

43. GouldEA

BuckleyA

1989 Antibody-dependent enhancement of yellow fever and Japanese encephalitis virus neurovirulence. J Gen Virol 70 (Pt 6) 1605 1608

44. BroomAK

WallaceMJ

MackenzieJS

SmithDW

HallRA

2000 Immunisation with gamma globulin to murray valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against australian encephalitis: evaluation in a mouse model. J Med Virol 61 259 265

45. WallaceMJ

SmithDW

BroomAK

MackenzieJS

HallRA

2003 Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice. J Gen Virol 84 1723 1728

46. TakanoT

KawakamiC

YamadaS

SatohR

HohdatsuT

2008 Antibody-dependent enhancement occurs upon re-infection with the identical serotype virus in feline infectious peritonitis virus infection. J Vet Med Sci 70 1315 1321

47. RothmanAL

2003 Immunology and immunopathogenesis of dengue disease. Adv Virus Res 60 397 419

48. VaughnDW

GreenS

KalayanaroojS

InnisBL

NimmannityaS

2000 Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 181 2 9

49. LibratyDH

YoungPR

PickeringD

EndyTP

KalayanaroojS

2002 High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis 186 1165 1168

50. LeitmeyerKC

VaughnDW

WattsDM

SalasR

Villalobos de ChaconI

1999 Dengue virus structural differences that correlate with pathogenesis. J Virol 73 4738 4747

51. SimmonsCP

ChauTN

ThuyTT

TuanNM

HoangDM

2007 Maternal antibody and viral factors in the pathogenesis of dengue virus in infants. J Infect Dis 196 416 424