#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection


The H5N1 highly pathogenic avian influenza virus has been circulating in poultry in Asia, the Middle East, and Africa since its first appearance in southern China in 1996. This virus occasionally infects humans with a high case mortality rate and poses a significant pandemic threat. Since neutralizing antibodies generally play a major role in protective immunity against influenza viruses, antibody therapy is a potential option for preventing highly lethal infection with the H5N1 virus in humans. Here we evaluated the protective potential of a human-mouse chimeric monoclonal antibody with strong neutralizing activity against H5N1 viruses in mouse and nonhuman primate models of lethal H5N1 virus infection. The therapeutic use of the neutralizing antibody resulted in reduced viral loads and improved survival in animals infected with highly pathogenic H5N1 viruses. It was noted that the protective effects were more prominent in immunosuppressed macaques, which might provide a model of protection against severe clinical disease in immunocompromised patients. In addition, combination therapy together with an antiviral drug reduced the selection of escape mutants. Collectively, this study suggests that antibody therapy may have beneficial effects in clinical cases of H5N1 HPAI virus infection in humans.


Vyšlo v časopise: Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004192
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004192

Souhrn

The H5N1 highly pathogenic avian influenza virus has been circulating in poultry in Asia, the Middle East, and Africa since its first appearance in southern China in 1996. This virus occasionally infects humans with a high case mortality rate and poses a significant pandemic threat. Since neutralizing antibodies generally play a major role in protective immunity against influenza viruses, antibody therapy is a potential option for preventing highly lethal infection with the H5N1 virus in humans. Here we evaluated the protective potential of a human-mouse chimeric monoclonal antibody with strong neutralizing activity against H5N1 viruses in mouse and nonhuman primate models of lethal H5N1 virus infection. The therapeutic use of the neutralizing antibody resulted in reduced viral loads and improved survival in animals infected with highly pathogenic H5N1 viruses. It was noted that the protective effects were more prominent in immunosuppressed macaques, which might provide a model of protection against severe clinical disease in immunocompromised patients. In addition, combination therapy together with an antiviral drug reduced the selection of escape mutants. Collectively, this study suggests that antibody therapy may have beneficial effects in clinical cases of H5N1 HPAI virus infection in humans.


Zdroje

1. WebsterRG, BeanWJ, GormanOT, ChambersTM, KawaokaY (1992) Evolution and ecology of influenza A viruses. Microbiol Rev 56: 152–179.

2. RohmC, ZhouN, SussJ, MackenzieJ, WebsterRG (1996) Characterization of a novel influenza hemagglutinin, H15: criteria for determination of influenza A subtypes. Virology 217: 508–516.

3. FouchierRA, MunsterV, WallenstenA, BestebroerTM, HerfstS, et al. (2005) Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol 79: 2814–2822.

4. LiKS, GuanY, WangJ, SmithGJD, XuKM, et al. (2004) Genesis of highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 430: 209–213.

5. ChenH, SmithGJD, ZhangSY, QinK, WangJ, LiKS, et al. (2005) H5N1 virus outbreak in migratory waterfowl. Nature 436: 191–192.

6. DucatezMF, OlingerCM, OwoadeAA, De LandtsheerS, AmmerlaanW, et al. (2006) Avian flu: multiple introductions of H5N1 in Nigeria. Nature 442: 37.

7. SmithGJD, FanXH, WangJ, LiKS, QinK, et al. (2006) Emergence and predominance of an H5N1 influenza variant in China. Proc Natl Acad Sci USA 103: 16936–16941.

8. WangG, ZhanD, LiL, LeiF, LiuB, et al. (2008) H5N1 avian influenza re-emergence of Lake Qinghai: phylogenetic and antigenic analyses of the newly isolated viruses and roles of migratory birds in virus circulation. J Gen Virol 89: 697–702.

9. KajiharaM, MatsunoK, SimulunduE, MuramatsuM, NoyoriO, et al. (2011) An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration. Jpn J Vet Res 59: 89–100.

10. SakodaY, ItoH, UchidaY, OkamatsuM, YamamotoN, et al. (2012) Reintroduction of H5N1 highly pathogenic avian influenza virus by migratory water birds, causing poultry outbreaks in the 2010–2011 winter season in Japan. J Gen Virol 93: 541–550.

11. GambottoA, Barratt-BoyesSM, de JongMD, NeumannG, KawaokaY (2008) Human infection with highly pathogenic H5N1 influenza virus. Lancet 371: 1464–1475.

12. WHO. (2013) Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO. Available: http://www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/index.html. Accessed 14 May 2014.

13. KlenkHD, GartenW, MatrosovichM (2011) Molecular mechanisms of inter-species transmission and pathogenicity of influenza viruses: lessons from the 2009 pandemic. BioEssays 33: 180–188.

14. BothL, BanyardAC, van DolleweerdC, WrightE, MaJK, FooksAR (2013) Monoclonal antibodies for prophylactic and therapeutic use against viral infections. Vaccine 31: 1553–1559.

15. GoudsmitJ, MarissenWE, WeldonWC, NiezgodaM, HanlonCA, et al. (2006) Comparison of an anti-rabies human monoclonal antibody combination with human polyclonal anti-rabies immune globulin. J Infect Dis 193: 796–801.

16. MüllerT, DietzscholdB, ErtlH, FooksAR, FreulingC, et al. (2009) Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans. PLoS Negl Trop Dis 3: e542.

17. ProsniakM, FaberM, HanlonCA, RupprechtCE, HooperDC, DietzscholdB (2003) Development of a cocktail of recombinant-expressed human rabies virus-neutralizing monoclonal antibodies for postexposure prophylaxis of rabies. J Infect Dis 188: 53–56.

18. ter MeulenJ, BakkerAB, van den BrinkEN, WeverlingGJ, MartinaBE, et al. (2004) Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet 363: 2139–2141.

19. ter MeulenJ, van den BrinkEN, PoonLL, MarissenWE, LeungCS, et al. (2006) Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med 3: e237.

20. BossartKN, GeisbertTW, FeldmannH, ZhuZ, FeldmannF, et al. (2011) A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge. Sci Transl Med 3: 105ra103.

21. BossartKN, RockxB, FeldmannF, BriningD, ScottD, et al. (2012) A Hendra virus G glycoprotein subunit vaccine protects African green monkeys from Nipah virus challenge. Sci Transl Med 4: 146ra107.

22. DyeJM, HerbertAS, KuehneAI, BarthJF, MuhammadMA, et al. (2012) Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease. Proc Natl Acad Sci USA 109: 5034–5039.

23. MarziA, YoshidaR, MiyamotoH, IshijimaM, SuzukiY, et al. (2012) Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever. PLoS One 7: e36192.

24. QiuX, AudetJ, WongG, PilletS, BelloA, et al. (2012) Successful treatment of ebola virus-infected cynomolgus macaques with monoclonal antibodies. Sci Transl Med 4: 138ra81.

25. OlingerGGJr, PettittJ, KimD, WorkingC, BohorovO, et al. (2012) Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proc Natl Acad Sci USA 109: 18030–18035.

26. KreijtzJH, FouchierRA, RimmelzwaanGF (2011) Immune responses to influenza virus infection. Virus Res 162: 19–30.

27. LeQM, ItoM, MuramotoY, HoangPV, VuongCD, et al. (2010) Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam. J Gen Virol 91: 2485–2490.

28. ReedLJ, MuenchH (1938) A simple method of estimating fifty percent endpoints. Am J Hyg 27: 493–497.

29. PhamVL, NakayamaM, ItohY, IshigakiH, KitanoM, et al. (2013) Pathogenicity of pandemic H1N1 influenza A virus in immunocompromised cynomolgus macaques. PLoS One 8: e75910.

30. KitanoM, ItohY, KodamaM, IshigakiH, NakayamaM, et al. (2011) Efficacy of single intravenous injection of peramivir against influenza B virus infection in ferrets and cynomolgus macaques. Antimicrob Agents Chemother 55: 4961–4970.

31. DanielsPS, JeffriesS, YatesP, SchildGC, RogersGN, et al. (1987) The receptor-binding and membrane-fusion properties of influenza virus variants selected using anti-haemagglutinin monoclonal antibodies. EMBO J 6: 1459–1465.

32. EisenMB, SabesanS, SkehelJJ, WileyDC (1997) Binding of the influenza A virus to cell-surface receptors: structures of five hemagglutinin-sialyloligosaccharide complexes determined by X-ray crystallography. Virology 232: 19–31.

33. RussellRJ, StevensDJ, HaireLF, GamblinSJ, SkehelJJ (2006) Avian and human receptor binding by hemagglutinins of influenza A viruses. Glycoconj J 23: 85–92.

34. HaY, StevensDJ, SkehelJJ, WileyDC (2001) X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs. Proc Natl Acad Sci USA 98: 11181–11186.

35. HattaM, GaoP, HalfmannP, KawaokaY (2001) Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293: 1840–1842.

36. ParkCH, IshinakaM, TakadaA, KidaH, KimuraT, et al. (2002) The invasion routes of neurovirulent A/Hong Kong/483/97 (H5N1) influenza virus into the central nervous system after respiratory infection in mice. Arch Virol 147: 1425–1436.

37. NakayamaM, ShichinoheS, ItohY, IshigakiH, KitanoM, et al. (2013) Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine. PLoS ONE 8: e82740.

38. WuC, LuX, WangX, JinT, ChengX, et al. (2013) Clinical symptoms, immune factors, and molecular characteristics of an adult male in Shenzhen, China infected with influenza virus H5N1. J Med Virol 85: 760–768.

39. NakajimaN, Van TinN, SatoY, ThachHN, KatanoH, et al. (2013) Pathological study of archival lung tissues from five fatal cases of avian H5N1 influenza in Vietnam. Mod Pathol 26: 357–369.

40. de JongMD, ThanhTT, KhanhTH, HienVM, SmithGJD, et al. (2005) Oseltamivir Resistance during Treatment of Influenza A (H5N1) Infection. N Engl J Med 353: 2667–2672.

41. LeQM, KisoM, SomeyaK, SakaiYT, NguyenTH, et al. (2005) Avian flu: Isolation of drug-resistant H5N1 virus. Nature 437: 1108–1108.

42. BoltzDA, DouangngeunB, PhommachanhP, SinthasakS, MondryR, et al. (2010) Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People's Democratic Republic. J Gen Virol 91 (Pt 4) 949–959.

43. ZhouB, ZhongN, GuanY (2007) Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med 357: 1450–1451.

44. ChenY, QinK, WuWL, LiG, ZhangJ, et al. (2009) Broad cross-protection against H5N1 avian influenza virus infection by means of monoclonal antibodies that map to conserved viral epitopes. J Infect Dis 199: 49–58.

45. OhHL, AkerströmS, ShenS, BereczkyS, KarlbergH, et al. (2010) An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 influenza viruses. J Virol 84: 8275–8286.

46. CortiD, VossJ, GamblinSJ, CodoniG, MacagnoA, et al. (2011) A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333: 850–856.

47. HansonBJ, BoonAC, LimAP, WebbA, OoiEE, et al. (2006) Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza A H5 hemagglutinin in mice. Respir Res 7: 126.

48. ManeewatchS, ThanongsaksrikulJ, SongsermT, Thueng-InK, KulkeawK, et al. (2009) Human single-chain antibodies that neutralize homologous and heterologous strains and clades of influenza A virus subtype H5N1. Antivir Ther 14: 221–230.

49. SuiJ, HwangWC, PerezS, WeiG, AirdD, et al. (2009) Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 16: 265–273.

50. van den BrandJM, HaagmansBL, van RielD, OsterhausAD, KuikenT (2014) The Pathology and Pathogenesis of Experimental Severe Acute Respiratory Syndrome and Influenza in Animal Models. J Comp Pathol (in press).

51. PrabakaranM, PrabhuN, HeF, HongliangQ, HoHT, et al. (2009) Combination therapy using chimeric monoclonal antibodies protects mice from lethal H5N1 infection and prevents formation of escape mutants. PLoS One 4: e5672.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#