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Characteristics of Memory B Cells Elicited by a Highly Efficacious HPV Vaccine in Subjects with No Pre-existing Immunity


There is an urgent need to better understand how to reliably generate effective vaccines, particularly subunit vaccines, as certain pathogens are considered to pose too great of a safety risk to be developed as live, attenuated or killed vaccines (e.g., HIV-1). The human papillomavirus (HPV) vaccines are two of the most effective subunit vaccines ever developed and have continued to show protection against HPV associated disease up to and beyond five years post-vaccination. Moreover, the target population for these vaccines have essentially no pre-existing immunity to the HPV types covered by the vaccine; therefore, these vaccines provide an excellent model for studying the immunity elicited by a highly effective subunit vaccine. As the HPV vaccines, like most vaccines, protect by generating antibodies, we are interested in characterizing the memory B cells elicited by the HPV vaccine. Memory B cells help to sustain antibody levels over time by rapidly differentiating into antibody secreting cells upon pathogen re-exposure. Although previous studies have provided evidence that the HPV vaccines elicit memory B cells, they did not characterize these cells. Here, we have isolated HPV-specific memory B cells from adolescent females and women who received the quadrivalent HPV vaccine and have cloned antibodies from these cells. Importantly, we find that these antibodies potently inhibit HPV and that the memory B cells from which they derive exhibit hallmarks of long-lived memory B cells.


Vyšlo v časopise: Characteristics of Memory B Cells Elicited by a Highly Efficacious HPV Vaccine in Subjects with No Pre-existing Immunity. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004461
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004461

Souhrn

There is an urgent need to better understand how to reliably generate effective vaccines, particularly subunit vaccines, as certain pathogens are considered to pose too great of a safety risk to be developed as live, attenuated or killed vaccines (e.g., HIV-1). The human papillomavirus (HPV) vaccines are two of the most effective subunit vaccines ever developed and have continued to show protection against HPV associated disease up to and beyond five years post-vaccination. Moreover, the target population for these vaccines have essentially no pre-existing immunity to the HPV types covered by the vaccine; therefore, these vaccines provide an excellent model for studying the immunity elicited by a highly effective subunit vaccine. As the HPV vaccines, like most vaccines, protect by generating antibodies, we are interested in characterizing the memory B cells elicited by the HPV vaccine. Memory B cells help to sustain antibody levels over time by rapidly differentiating into antibody secreting cells upon pathogen re-exposure. Although previous studies have provided evidence that the HPV vaccines elicit memory B cells, they did not characterize these cells. Here, we have isolated HPV-specific memory B cells from adolescent females and women who received the quadrivalent HPV vaccine and have cloned antibodies from these cells. Importantly, we find that these antibodies potently inhibit HPV and that the memory B cells from which they derive exhibit hallmarks of long-lived memory B cells.


Zdroje

1. MunozN, KjaerSK, SigurdssonK, IversenOE, Hernandez-AvilaM, et al. (2010) Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women. J Natl Cancer Inst 102: 325–339.

2. GiulianoAR, PalefskyJM, GoldstoneS, MoreiraEDJr, PennyME, et al. (2011) Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med 364: 401–411.

3. PalefskyJM, GiulianoAR, GoldstoneS, MoreiraEDJr, ArandaC, et al. (2011) HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 365: 1576–1585.

4. BoschFX, TsuV, VorstersA, Van DammeP, KaneMA (2012) Reframing cervical cancer prevention. Expanding the field towards prevention of human papillomavirus infections and related diseases. Vaccine 30 Suppl 5: F1–11.

5. GarlandSM, Hernandez-AvilaM, WheelerCM, PerezG, HarperDM, et al. (2007) Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. The New England journal of medicine 356: 1928–1943.

6. The Future II Study Group (2007) Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. The New England journal of medicine 356: 1915–1927.

7. JouraEA, KjaerSK, WheelerCM, SigurdssonK, IversenOE, et al. (2008) HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine. Vaccine 26: 6844–6851.

8. BreitburdF, KirnbauerR, HubbertNL, NonnenmacherB, Trin-Dinh-DesmarquetC, et al. (1995) Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. J Virol 69: 3959–3963.

9. DayPM, KinesRC, ThompsonCD, JaguS, RodenRB, et al. (2010) In vivo mechanisms of vaccine-induced protection against HPV infection. Cell Host Microbe 8: 260–270.

10. SuzichJA, GhimSJ, Palmer-HillFJ, WhiteWI, TamuraJK, et al. (1995) Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas. Proc Natl Acad Sci U S A 92: 11553–11557.

11. PlotkinSA (2008) Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis 47: 401–409.

12. VictoraGD, NussenzweigMC (2012) Germinal centers. Annu Rev Immunol 30: 429–457.

13. VillaLL, CostaRL, PettaCA, AndradeRP, PaavonenJ, et al. (2006) High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 95: 1459–1466.

14. OlssonSE, VillaLL, CostaRL, PettaCA, AndradeRP, et al. (2007) Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine 25: 4931–4939.

15. EinsteinMH, BaronM, LevinMJ, ChatterjeeA, FoxB, et al. (2011) Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12–24 in a Phase III randomized study of healthy women aged 18–45 years. Hum Vaccin 7: 1343–1358.

16. DoucettVP, GerhardW, OwlerK, CurryD, BrownL, et al. (2005) Enumeration and characterization of virus-specific B cells by multicolor flow cytometry. Journal of immunological methods 303: 40–52.

17. TianC, LuskinGK, DischertKM, HigginbothamJN, ShepherdBE, et al. (2008) Immunodominance of the VH1-46 antibody gene segment in the primary repertoire of human rotavirus-specific B cells is reduced in the memory compartment through somatic mutation of nondominant clones. Journal of immunology 180: 3279–3288.

18. HicarMD, ChenX, BrineyB, HammondsJ, WangJJ, et al. (2010) Pseudovirion particles bearing native HIV envelope trimers facilitate a novel method for generating human neutralizing monoclonal antibodies against HIV. J Acquir Immune Defic Syndr 54: 223–235.

19. BuckCB, ChengN, ThompsonCD, LowyDR, StevenAC, et al. (2008) Arrangement of L2 within the papillomavirus capsid. Journal of virology 82: 5190–5197.

20. BuckCB, PastranaDV, LowyDR, SchillerJT (2005) Generation of HPV pseudovirions using transfection and their use in neutralization assays. Methods Mol Med 119: 445–462.

21. CrottyS, AubertRD, GlidewellJ, AhmedR (2004) Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system. J Immunol Methods 286: 111–122.

22. KleinU, RajewskyK, KuppersR (1998) Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med 188: 1679–1689.

23. AgematsuK, NagumoH, YangFC, NakazawaT, FukushimaK, et al. (1997) B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production. Eur J Immunol 27: 2073–2079.

24. BrochetX, LefrancMP, GiudicelliV (2008) IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res 36: W503–508.

25. DayPM, ThompsonCD, BuckCB, PangYY, LowyDR, et al. (2007) Neutralization of human papillomavirus with monoclonal antibodies reveals different mechanisms of inhibition. Journal of virology 81: 8784–8792.

26. ChristensenND, DillnerJ, EklundC, CarterJJ, WipfGC, et al. (1996) Surface conformational and linear epitopes on HPV-16 and HPV-18 L1 virus-like particles as defined by monoclonal antibodies. Virology 223: 174–184.

27. RodenRB, WeissingerEM, HendersonDW, BooyF, KirnbauerR, et al. (1994) Neutralization of bovine papillomavirus by antibodies to L1 and L2 capsid proteins. J Virol 68: 7570–7574.

28. HicarMD, KalamsSA, SpearmanPW, CroweJEJr (2010) Emerging studies of human HIV-specific antibody repertoires. Vaccine 28 Suppl 2: : B18–23.

29. CulpTD, SpatzCM, ReedCA, ChristensenND (2007) Binding and neutralization efficiencies of monoclonal antibodies, Fab fragments, and scFv specific for L1 epitopes on the capsid of infectious HPV particles. Virology 361: 435–446.

30. PastranaDV, TolstovYL, BeckerJC, MoorePS, ChangY, et al. (2009) Quantitation of human seroresponsiveness to Merkel cell polyomavirus. PLoS Pathog 5: e1000578.

31. StanleyM, PintoLA, TrimbleC (2012) Human papillomavirus vaccines–immune responses. Vaccine 30 Suppl 5: : F83–87.

32. RodenRB, HubbertNL, KirnbauerR, ChristensenND, LowyDR, et al. (1996) Assessment of the serological relatedness of genital human papillomaviruses by hemagglutination inhibition. Journal of virology 70: 3298–3301.

33. LeggatDJ, ThompsonRS, KhaskhelyNM, IyerAS, WesterinkMA (2013) The immune response to pneumococcal polysaccharides 14 and 23F among elderly individuals consists predominantly of switched memory B cells. The Journal of infectious diseases 208: 101–108.

34. FranzB, MayKFJr, DranoffG, WucherpfennigK (2011) Ex vivo characterization and isolation of rare memory B cells with antigen tetramers. Blood 118: 348–357.

35. SmolenKK, GelinasL, FranzenL, DobsonS, DawarM, et al. (2012) Age of recipient and number of doses differentially impact human B and T cell immune memory responses to HPV vaccination. Vaccine 30: 3572–3579.

36. KarlssonAC, MartinJN, YoungerSR, BredtBM, EplingL, et al. (2003) Comparison of the ELISPOT and cytokine flow cytometry assays for the enumeration of antigen-specific T cells. Journal of immunological methods 283: 141–153.

37. ScheidJF, MouquetH, UeberheideB, DiskinR, KleinF, et al. (2011) Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333: 1633–1637.

38. MouquetH, ScharfL, EulerZ, LiuY, EdenC, et al. (2012) Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A 109: E3268–3277.

39. FrolichD, GieseckeC, MeiHE, ReiterK, DaridonC, et al. (2010) Secondary immunization generates clonally related antigen-specific plasma cells and memory B cells. Journal of immunology 185: 3103–3110.

40. JiangN, HeJ, WeinsteinJA, PenlandL, SasakiS, et al. (2013) Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med 5: 171ra119.

41. HuoZ, BissettSL, GiemzaR, BeddowsS, OeserC, et al. (2012) Systemic and mucosal immune responses to sublingual or intramuscular human papilloma virus antigens in healthy female volunteers. PLoS One 7: e33736.

42. TillerT, TsuijiM, YurasovS, VelinzonK, NussenzweigMC, et al. (2007) Autoreactivity in human IgG+ memory B cells. Immunity 26: 205–213.

43. WalkerLM, PhogatSK, Chan-HuiPY, WagnerD, PhungP, et al. (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326: 285–289.

44. WuX, YangZY, LiY, HogerkorpCM, SchiefWR, et al. (2010) Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329: 856–861.

45. WrammertJ, SmithK, MillerJ, LangleyWA, KokkoK, et al. (2008) Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 453: 667–671.

46. KleinF, DiskinR, ScheidJF, GaeblerC, MouquetH, et al. (2013) Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell 153: 126–138.

47. BurtonDR, AhmedR, BarouchDH, ButeraST, CrottyS, et al. (2012) A Blueprint for HIV Vaccine Discovery. Cell Host Microbe 12: 396–407.

48. WuX, ZhouT, ZhuJ, ZhangB, GeorgievI, et al. (2011) Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science 333: 1593–1602.

49. HuangCC, VenturiM, MajeedS, MooreMJ, PhogatS, et al. (2004) Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120. Proceedings of the National Academy of Sciences of the United States of America 101: 2706–2711.

50. WrammertJ, KoutsonanosD, LiGM, EdupugantiS, SuiJ, et al. (2011) Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. The Journal of experimental medicine 208: 181–193.

51. DayPM, LowyDR, SchillerJT (2003) Papillomaviruses infect cells via a clathrin-dependent pathway. Virology 307: 1–11.

52. SelinkaHC, GiroglouT, NowakT, ChristensenND, SappM (2003) Further evidence that papillomavirus capsids exist in two distinct conformations. Journal of virology 77: 12961–12967.

53. Blanchard-RohnerG, PulickalAS, Jol-van der ZijdeCM, SnapeMD, PollardAJ (2009) Appearance of peripheral blood plasma cells and memory B cells in a primary and secondary immune response in humans. Blood 114: 4998–5002.

54. WismansPJ, van HattumJ, MuddeGC, EndemanHJ, PoelJ, et al. (1989) Is booster injection with hepatitis B vaccine necessary in healthy responders? A study of the immune response. J Hepatol 8: 236–240.

55. LavinderJJ, WineY, GieseckeC, IppolitoGC, HortonAP, et al. (2014) Identification and characterization of the constituent human serum antibodies elicited by vaccination. Proceedings of the National Academy of Sciences of the United States of America 111: 2259–2264.

56. AmannaIJ, CarlsonNE, SlifkaMK (2007) Duration of humoral immunity to common viral and vaccine antigens. N Engl J Med 357: 1903–1915.

57. DobsonSR, McNeilS, DionneM, DawarM, OgilvieG, et al. (2013) Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. Jama 309: 1793–1802.

58. SchneiderCA, RasbandWS, EliceiriKW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9: 671–675.

59. PerfettoSP, ChattopadhyayPK, LamoreauxL, NguyenR, AmbrozakD, et al. (2010) Amine-reactive dyes for dead cell discrimination in fixed samples. Curr Protoc Cytom Chapter 9: Unit 9 34.

60. WardemannH, YurasovS, SchaeferA, YoungJW, MeffreE, et al. (2003) Predominant autoantibody production by early human B cell precursors. Science 301: 1374–1377.

61. LebecqueSG, GearhartPJ (1990) Boundaries of somatic mutation in rearranged immunoglobulin genes: 5′ boundary is near the promoter, and 3′ boundary is approximately 1 kb from V(D)J gene. J Exp Med 172: 1717–1727.

62. RogersonBJ (1994) Mapping the upstream boundary of somatic mutations in rearranged immunoglobulin transgenes and endogenous genes. Mol Immunol 31: 83–98.

63. RadaC, Gonzalez-FernandezA, JarvisJM, MilsteinC (1994) The 5′ boundary of somatic hypermutation in a V kappa gene is in the leader intron. European journal of immunology 24: 1453–1457.

64. Di NoiaJM, NeubergerMS (2007) Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem 76: 1–22.

65. SmithK, GarmanL, WrammertJ, ZhengNY, CapraJD, et al. (2009) Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen. Nat Protoc 4: 372–384.

66. GiudicelliV, DurouxP, GinestouxC, FolchG, Jabado-MichaloudJ, et al. (2006) IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences. Nucleic acids research 34: D781–784.

67. GiudicelliV, ChaumeD, LefrancMP (2005) IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic acids research 33: D256–261.

68. LiaoHX, LevesqueMC, NagelA, DixonA, ZhangR, et al. (2009) High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies. J Virol Methods 158: 171–179.

69. WangX, StollarBD (2000) Human immunoglobulin variable region gene analysis by single cell RT-PCR. Journal of immunological methods 244: 217–225.

70. TillerT, MeffreE, YurasovS, TsuijiM, NussenzweigMC, et al. (2008) Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J Immunol Methods 329: 112–124.

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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