Lower Baseline Germinal Center Activity and Preserved Th1 Immunity are Associated with Hepatitis B Vaccine Response in Treated HIV Infection
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Abstract
Background: Why HIV-infected individuals have poor responses to standard dose and schedule hepatitis B virus immunization is not well understood.
Methods: We compared the serologic and cellular immune profiles of treated HIV-infected individuals with similar durations of infection and preserved CD4 counts (>350 cells/microliter) by hepatitis B vaccine (HBV) response before and after vaccination.
Results: Similar levels of immune activation and plasma cytokine profile were found between non-responders and responders. The baseline plasma levels of CXCL-13, a surrogate of germinal center reactivity, were significantly lower in HBV responders compared to HBV non-responders and were a predictor of both vaccine response and titer. Furthermore, response to HBV vaccination was associated with a significantly higher frequency of circulating IgGhigh memory B cells post vaccination and preserved Th1 antigen-specific T-cell responses.
Conclusions: Taken together, our data suggest that preserved Th1 responses are associated with hepatitis B vaccine response in treated HIV infection.
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References
1. Poland GA, Jacobson RM. Clinical practice: prevention of hepatitis B with the hepatitis B vaccine. N Engl J Med. 2004;351(27):2832-8. PubMed PMID: 15625334. doi: 10.1056/NEJMcp041507
2. Alper CA, Kruskall MS, Marcus-Bagley D, Craven DE, Katz AJ, Brink SJ, Dienstag JL, Awdeh Z, Yunis EJ. Genetic prediction of nonresponse to hepatitis B vaccine. N Engl J Med. 1989;321(11):708-12.
3. Hohler T, Reuss E, Evers N, Dietrich E, Rittner C, Freitag CM, Vollmar J, Schneider PM, Fimmers R. Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins. Lancet. 2002;360(9338):991-5.
4. Landrum ML, Hullsiek KH, Chun HM, Crum-Cianflone NF, Ganesan A, Weintrob AC, Barthel RV, O’Connell RJ, Agan BK. The timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and the risk of HBV infection following HIV diagnosis. Am J Epidemiol. 2011;173(1):84-93. PubMed PMID: 21051446. Pubmed Central PMCID: 3025642. doi: 10.1093/aje/kwq326
5. Landrum ML, Hullsiek KH, Ganesan A, Weintrob AC, Crum-Cianflone NF, Barthel RV, O’Connell RJ, Fieberg A, Chun HM, Marconi VC, Dolan MJ, Agan BK. Hepatitis B vaccination and risk of hepatitis B infection in HIV-infected individuals. AIDS. 2010;24(4):545-55. PubMed PMID: 19487908. Pubmed Central PMCID: 2831117. doi: 10.1097/QAD.0b013e32832cd99e
6. del Pozo Balado Mdel M, Leal M, Mendez Lagares G, Mata RC, Lopez-Cortes LF, Viciana P, Pacheco YM. Increased regulatory T cell counts in HIV-infected nonresponders to hepatitis B virus vaccine. J Infect Dis. 2010;202(3):362-9. PubMed PMID: 20560766. doi: 10.1086/653707
7. Kroon FP, van Dissel JT, de Jong JC, Zwinderman K, van Furth R. Antibody response after influenza vaccination in HIV-infected individuals: a consecutive 3-year study. Vaccine. 2000;18(26):3040-9. PubMed PMID: 10825608.
8. Launay O, Desaint C, Durier C, Loulergue P, Duval X, Jacomet C, Pialoux G, Ghosn J, Raffi F, Rey D, Ajana F, Colin de Verdière N, Reynes J, Foubert V, Roman F, Devaster JM, Delfraissy JF, Aboulker JP. Safety and Immunogenicity of a Monovalent 2009 Influenza A/H1N1v Vaccine Adjuvanted With AS03A or Unadjuvanted in HIV-Infected Adults: A Randomized, Controlled Trial. J Infect Dis. 2011;204(1):124-34. PubMed PMID: 21628666. Pubmed Central PMCID: 3307156. doi: 10.1093/infdis/jir211
9. Pallikkuth S, Parmigiani A, Silva SY, George VK, Fischl M, Pahwa R, Pahwa S. Impaired peripheral blood T follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine. Blood. 2012;120(5):985-93. PubMed PMID: 22692510. doi: 10.1182/blood-2011-12-396648
10. Tasker SA, Treanor JJ, Paxton WB, Wallace MR. Efficacy of influenza vaccination in HIV-infected persons. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;131(6):430-3. PubMed PMID: 10498559.
11. Launay O, van der Vliet D, Rosenberg AR, Michel ML, Piroth L, Rey D, Colin de Verdi ère N, Slama L, Martin K, Lortholary O, Carrat F, Trial AHV-B. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA. 2011;305(14):1432-40. PubMed PMID: 21486976. doi: 10.1001/jama.2011.351
12. Malaspina A, Moir S, Orsega SM, Vasquez J, Miller NJ, Donoghue ET, Kottilil S, Gezmu M, Follmann D, Vodeiko GM, Levandowski RA, Mican JM, Fauci AS. Compromised B cell responses to influenza vaccination in HIV-infected individuals. J Infect Dis. 2005;191(9):1442-50. PubMed PMID: 15809902. doi: 10.1086/429298
13. De Milito A, Morch C, Sonnerborg A, Chiodi F. Loss of memory (CD27) B lymphocytes in HIV-1 infection. AIDS. 2001;15(8):957-64. PubMed PMID: 11399977.
14. De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, Grutzmeier S, Sonnerborg A, Chiodi F. Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood. 2004;103(6):2180-6. PubMed PMID: 14604962. doi: 10.1182/blood-2003-07-2375
15. Cagigi A, Nilsson A, Pensieroso S, Chiodi F. Dysfunctional B-cell responses during HIV-1 infection: implication for influenza vaccination and highly active antiretroviral therapy. Lancet Infect Dis. 2010;10(7):499-503. PubMed PMID: 20610332. doi: 10.1016/S1473-3099(10)70117-1
16. Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, O’Shea MA, Roby G, Kottilil S, Arthos J, Proschan MA, Chun TW, Fauci AS. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med. 2008;205(8):1797-805. PubMed PMID: 18625747. Pubmed Central PMCID: 2525604. doi: 10.1084/jem.20072683
17. He B, Qiao X, Klasse PJ, Chiu A, Chadburn A, Knowles DM, Moore JP, Cerutti A. HIV-1 envelope triggers polyclonal Ig class switch recombination through a CD40-independent mechanism involving BAFF and C-type lectin receptors. J Immunol. 2006;176(7):3931-41. PubMed PMID: 16547227.
18. Vinuesa CG, Cyster JG. How T cells earn the follicular rite of passage. Immunity. 2011;35(5):671-80. PubMed PMID: 22118524. doi: 10.1016/j.immuni.2011.11.001
19. Boswell KL, Paris R, Boritz E, Ambrozak D, Yamamoto T, Darko S, Wloka K, Wheatley A, Narpala S, McDermott A, Roederer M, Haubrich R, Connors M, Ake J, Douek DC, Kim J, Petrovas C, Koup RA. Loss of Circulating CD4 T Cells with B Cell Helper Function during Chronic HIV Infection. PLoS Pathog. 2014;10(1):e1003853. PubMed PMID: 24497824. doi: 10.1371/journal.ppat.1003853
20. Paris RM, Petrovas C, Ferrando-Martinez S, Moysi E, Boswell KL, Archer E, Yamamoto T, Ambrozak D, Casazza JP, Haubrich R, Connors M, Ake J, Kim JH, Koup RA. Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression. PLoS One. 2015;10(12):e0144767. PubMed PMID: 26678998. doi: 10.1371/journal.pone.0144767
21. Okulicz JF, Marconi VC, Landrum ML, Wegner S, Weintrob A, Ganesan A, Hale B, Crum-Cianflone N, Delmar J, Barthel V, Quinnan G, Agan BK, Dolan MJ. Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of Defense HIV natural history study. J Infect Dis. 2009;200(11):1714-23. PubMed PMID: 19852669. doi: 10.1086/646609
22. Chun HM, Fieberg AM, Hullsiek KH, Lifson AR, Crum-Cianflone NF, Weintrob AC, Ganesan A, Barthel RV, Bradley WP, Agan BK, Landrum ML. Epidemiology of Hepatitis B virus infection in a US cohort of HIV-infected individuals during the past 20 years. Clin Infect Dis. 2010;50(3):426-36. PubMed PMID: 20047484. Pubmed Central PMCID: 2805765. doi: 10.1086/649885
23. Okulicz JF, Mesner O, Ganesan A, O’Bryan TA, Deiss RG, Agan BK. Hepatitis B vaccine responsiveness and clinical outcomes in HIV controllers. PLoS One. 2014;9(8):e105591. PubMed PMID: 25144773. Pubmed Central PMCID: Pmc4140789. doi: 10.1371/journal.pone.0105591
24. Reid MJ, Goetz DW, Zajac RA, Houk RW, Boswell RN. The natural history of human immunodeficiency virus infection in screened HIV positive U.S. Air Force personnel: a preliminary report. J Acquir Immune Defic Syndr. 1988;1(5):508-15.
25. Shive CL, Jiang W, Anthony DD, Lederman MM. Soluble CD14 is a nonspecific marker of monocyte activation. AIDS. 2015;29(10):1263-5. PubMed PMID: 26035325. Pubmed Central PMCID: PMC4452959. doi: 10.1097/QAD.0000000000000735
26. Havenar-Daughton C, Lindqvist M, Heit A, Wu JE, Reiss SM, Kendric K, Belanger S, Kasturi SP, Landais E, Akondy RS, McGuire HM, Bothwell M, Vagefi PA, Scully E, Investigators IPCP, Tomaras GD, Davis MM, Poignard P, Ahmed R, Walker BD, Pulendran B, McElrath MJ, Kaufmann DE, Crotty S. CXCL13 is a plasma biomarker of germinal center activity. Proc Natl Acad Sci U S A. 2016;113(10):2702-7. PubMed PMID: 26908875. Pubmed Central PMCID: PMC4790995. doi: 10.1073/pnas.1520112113
27. Okada T, Ngo VN, Ekland EH, Förster R, Lipp M, Littman DR, Cyster JG. Chemokine Requirements for B Cell Entry to Lymph Nodes and Peyer’s Patches. J Exp Med. 2002;196(1):65-75. doi: 10.1084/jem.20020201
28. Gunn MD, Ngo VN, Ansel KM, Ekland EH, Cyster JG, Williams LT. A B-cell-homing chemokine made in lymphoid follicles activates Burkitt’s lymphoma receptor-1. Nature. 1998;391(6669):799-803. PubMed PMID: 9486651. doi: 10.1038/35876
29. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011;34(1):108-21. PubMed PMID: 21215658. Pubmed Central PMCID: 3046815. S1074-7613(10)00491-7 [pii] doi: 10.1016/j.immuni.2010.12.012
30. Hsieh C, Macatonia S, Tripp C, Wolf S, O’Garra A, Murphy K. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993;260(5107):547-9. doi: 10.1126/science.8097338
31. He R, Hou S, Liu C, Zhang A, Bai Q, Han M, Yang Y, Wei G, Shen T, Yang X, Xu L, Chen X, Hao Y, Wang P, Zhu C, Ou J, Liang H, Ni T, Zhang X, Zhou X, Deng K, Chen Y, Luo Y, Xu J, Qi H, Wu Y, Ye L. Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection. Nature. 2016. PubMed PMID: 27501245. doi: 10.1038/nature19317
32. Petrovas C, Ferrando-Martinez S, Gerner MY, Casazza JP, Pegu A, Deleage C, Cooper A, Hataye J, Andrews S, Ambrozak D, Del Río Estrada PM, Boritz E, Paris R, Moysi E, Boswell KL, Ruiz-Mateos E, Vagios I, Leal M, Ablanedo-Terrazas Y, Rivero A, Gonzalez-Hernandez LA, McDermott AB, Moir S, Reyes-Terán G, Docobo F, Pantaleo G, Douek DC, Betts MR, Estes JD, Germain RN, Mascola JR, Koup RA. Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Sci Transl Med. 2017;9(373). PubMed PMID: 28100833. doi: 10.1126/scitranslmed.aag2285
33. Leong YA, Chen Y, Ong HS, Wu D, Man K, Deleage C, Minnich M, Meckiff BJ, Wei Y, Hou Z, Zotos D, Fenix KA, Atnerkar A, Preston S, Chipman JG, Beilman GJ, Allison CC, Sun L, Wang P, Xu J, Toe JG, Lu HK, Tao Y, Palendira U, Dent AL, Landay AL, Pellegrini M, Comerford I, McColl SR, Schacker TW, Long HM, Estes JD, Busslinger M, Belz GT, Lewin SR, Kallies A, Yu D. CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles. Nat Immunol. 2016; advance online publication. doi: 10.1038/ni.3543. http://www.nature.com/ni/journal/vaop/ncurrent/abs/ni.3543.html#supplementary-information
34. Mehta N, Cunningham CK, Flynn P, Pepe J, Obaro S, Kapogiannis BG, Bethel J, Luzuriaga K, Adolescent Trials Network for HIVAI. Impaired generation of hepatitis B virus-specific memory B cells in HIV infected individuals following vaccination. Vaccine. 2010;28(21):3672-8. PubMed PMID: 20356567. Pubmed Central PMCID: 2862082. doi: 10.1016/j.vaccine.2010.03.022
35. Launay O, Rosenberg AR, Rey D, Pouget N, Michel ML, Reynes J, Neau D, Raffi F, Piroth L, Carrat F, Group AHV-B. Long-term immune response to hepatitis b virus vaccination regimens in adults with human immunodeficiency virus 1: Secondary analysis of a randomized clinical trial. JAMA Intern Med. 2016;176(5):603-10. PubMed PMID: 27064975. doi: 10.1001/jamainternmed.2016.0741
36. Rey D, Piroth L, Wendling MJ, Miailhes P, Michel ML, Dufour C, Haour G, Sogni P, Rohel A, Ajana F, Billaud E, Molina JM, Launay O, Carrat F. Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial. Lancet Infect Dis. 2015;15(11):1283-91. PubMed PMID: 26257021. doi: 10.1016/s1473-3099(15)00220-0
37. Chaiklang K, Wipasa J, Chaiwarith R, Praparattanapan J, Supparatpinyo K. Comparison of immunogenicity and safety of four doses and four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: a randomized, controlled trial. PLoS One. 2013;8(11):e80409. PubMed PMID: 24265819. Pubmed Central PMCID: PMC3827227. doi: 10.1371/journal.pone.0080409
38. Migueles SA, Connors M. Success and failure of the cellular immune response against HIV-1. Nat Immunol. 2015;16(6):563-70. PubMed PMID: 25988888. doi: 10.1038/ni.3161
39. Bart PA, Rizzardi GP, Tambussi G, Chave JP, Chapuis AG, Graziosi C, Corpataux JM, Halkic N, Meuwly JY, Munoz M, Meylan P, Spreen W, McDade H, Yerly S, Perrin L, Lazzarin A, Pantaleo G. Immunological and virological responses in HIV-1-infected adults at early stage of established infection treated with highly active antiretroviral therapy. AIDS. 2000;14(13):1887-97. PubMed PMID: 10997391.
40. Angel JB, Parato KG, Kumar A, Kravcik S, Badley AD, Fex C, Ashby D, Sun E, Cameron DW. Progressive human immunodeficiency virus-specific immune recovery with prolonged viral suppression. J Infect Dis. 2001;183(4):546-54. PubMed PMID: 11170979. doi: 10.1086/318547
41. Saito R, Onodera H, Tago H, Suzuki Y, Shimizu M, Matsumura Y, Kondo T, Itoyama Y. Altered expression of chemokine receptor CXCR5 on T cells of myasthenia gravis patients. J Neuroimmunol. 2005;170(1-2):172-8. PubMed PMID: 16214223. doi: 10.1016/j.jneuroim.2005.09.001
42. Payne D, Drinkwater S, Baretto R, Duddridge M, Browning MJ. Expression of chemokine receptors CXCR4, CXCR5 and CCR7 on B and T lymphocytes from patients with primary antibody deficiency. Clin Exp Immunol. 2009;156(2):254-62. PubMed PMID: 19250276. Pubmed Central PMCID: PMC2759473. doi: 10.1111/j.1365-2249.2009.03889.x
43. Mylvaganam GH, Rios D, Abdelaal HM, Iyer S, Tharp G, Mavinger M, Hicks S, Chahroudi A, Ahmed R, Bosinger SE, Williams IR, Skinner PJ, Velu V, Amara RR. Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection. Proc Natl Acad Sci U S A. 2017. PubMed PMID: 28159893. doi: 10.1073/pnas.1621418114