Effects of Chronic Viral Infection on Immune Response to Zoster Vaccination

Summary

This study aims to identify the innate and adaptive immune response to zoster vaccination. Half of the participants will be individuals with chronic hepatitis C, while the other half with healthy volunteers.The innate immune signature elicited by Zoster vaccination will be characterized by RNA-seq analysis of pre- and post-vaccination RNA from whole blood. We will compare fold changes in gene expression profiles pre- versus post-vaccination in each individual, as well as between the two arms of the study. RNA-seq will be used to assess innate immune activation by evaluating the changes to the expression levels of interferon-stimulated genes pre- and post-vaccination. Adaptive immune response will be determined by the traditional correlates of protection used in previous Zoster clinical studies in addition to flow cytometry24. Correlates of protection include antibody response, interferon gamma production and the frequency of responder cells post- vaccination24. For antibody production, we will perform Zoster glycoprotein ELISA (gpELISA) targeting IgG/IgM. The number and frequency of responder cells will be characterized by flow cytometry.

Timeline

Start

2015-12

Primary completion

2017-09-08

Completion

2017-09-08

Publications

• Background Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84. doi: 10.1056/NEJMoa051016.
• Background Lin F, Hadler JL. Epidemiology of primary varicella and herpes zoster hospitalizations: the pre-varicella vaccine era. J Infect Dis. 2000 Jun;181(6):1897-905. doi: 10.1086/315492. Epub 2000 Jun 5.
• Background Abu-Raddad LJ, Patnaik P, Kublin JG. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science. 2006 Dec 8;314(5805):1603-6. doi: 10.1126/science.1132338.
• Background Zhu J, Hladik F, Woodward A, Klock A, Peng T, Johnston C, Remington M, Magaret A, Koelle DM, Wald A, Corey L. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat Med. 2009 Aug;15(8):886-92. doi: 10.1038/nm.2006. Epub 2009 Aug 2.
• Background Pisell TL, Hoffman IF, Jere CS, Ballard SB, Molyneux ME, Butera ST, Lawn SD. Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection. AIDS. 2002 Jul 26;16(11):1503-9. doi: 10.1097/00002030-200207260-00007.
• Background Bahgat MM, El-Far MA, Mesalam AA, Ismaeil AA, Ibrahim AA, Gewaid HE, Maghraby AS, Ali MA, Abd-Elshafy DN. Schistosoma mansoni soluble egg antigens enhance HCV replication in mammalian cells. J Infect Dev Ctries. 2010 May 1;4(4):226-34. doi: 10.3855/jidc.522.
• Background Stelekati E, Wherry EJ. Chronic bystander infections and immunity to unrelated antigens. Cell Host Microbe. 2012 Oct 18;12(4):458-69. doi: 10.1016/j.chom.2012.10.001.
• Background Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011 Apr 28;472(7344):481-5. doi: 10.1038/nature09907. Epub 2011 Apr 10.
• Background Metz P, Dazert E, Ruggieri A, Mazur J, Kaderali L, Kaul A, Zeuge U, Windisch MP, Trippler M, Lohmann V, Binder M, Frese M, Bartenschlager R. Identification of type I and type II interferon-induced effectors controlling hepatitis C virus replication. Hepatology. 2012 Dec;56(6):2082-93. doi: 10.1002/hep.25908. Epub 2012 Oct 14.
• Background Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, Subramaniam S, Blattman JN, Barber DL, Ahmed R. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007 Oct;27(4):670-84. doi: 10.1016/j.immuni.2007.09.006. Epub 2007 Oct 18.
• Background Stelekati E, Shin H, Doering TA, Dolfi DV, Ziegler CG, Beiting DP, Dawson L, Liboon J, Wolski D, Ali MA, Katsikis PD, Shen H, Roos DS, Haining WN, Lauer GM, Wherry EJ. Bystander chronic infection negatively impacts development of CD8(+) T cell memory. Immunity. 2014 May 15;40(5):801-13. doi: 10.1016/j.immuni.2014.04.010.
• Background Urbani S, Amadei B, Tola D, Massari M, Schivazappa S, Missale G, Ferrari C. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J Virol. 2006 Nov;80(22):11398-403. doi: 10.1128/JVI.01177-06. Epub 2006 Sep 6.
• Background Moorman JP, Zhang CL, Ni L, Ma CJ, Zhang Y, Wu XY, Thayer P, Islam TM, Borthwick T, Yao ZQ. Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses. Vaccine. 2011 Apr 12;29(17):3169-76. doi: 10.1016/j.vaccine.2011.02.052. Epub 2011 Mar 3.
• Background Wiedmann M, Liebert UG, Oesen U, Porst H, Wiese M, Schroeder S, Halm U, Mossner J, Berr F. Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C. Hepatology. 2000 Jan;31(1):230-4. doi: 10.1002/hep.510310134.
• Background Crawford A, Angelosanto JM, Kao C, Doering TA, Odorizzi PM, Barnett BE, Wherry EJ. Molecular and transcriptional basis of CD4(+) T cell dysfunction during chronic infection. Immunity. 2014 Feb 20;40(2):289-302. doi: 10.1016/j.immuni.2014.01.005. Epub 2014 Feb 13.
• Background Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project. Nat Rev Immunol. 2012 Feb 17;12(3):191-200. doi: 10.1038/nri3158.
• Background Levin MJ, Smith JG, Kaufhold RM, Barber D, Hayward AR, Chan CY, Chan IS, Li DJ, Wang W, Keller PM, Shaw A, Silber JL, Schlienger K, Chalikonda I, Vessey SJ, Caulfield MJ. Decline in varicella-zoster virus (VZV)-specific cell-mediated immunity with increasing age and boosting with a high-dose VZV vaccine. J Infect Dis. 2003 Nov 1;188(9):1336-44. doi: 10.1086/379048. Epub 2003 Oct 17.
• Background Sauerbrei A, Wutzler P. Serological detection of varicella-zoster virus-specific immunoglobulin G by an enzyme-linked immunosorbent assay using glycoprotein antigen. J Clin Microbiol. 2006 Sep;44(9):3094-7. doi: 10.1128/JCM.00719-06.
• Background Soneson C, Delorenzi M. A comparison of methods for differential expression analysis of RNA-seq data. BMC Bioinformatics. 2013 Mar 9;14:91. doi: 10.1186/1471-2105-14-91.
• Background Law CW, Chen Y, Shi W, Smyth GK. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014 Feb 3;15(2):R29. doi: 10.1186/gb-2014-15-2-r29.
• Background Schmader KE, Johnson GR, Saddier P, Ciarleglio M, Wang WW, Zhang JH, Chan IS, Yeh SS, Levin MJ, Harbecke RM, Oxman MN; Shingles Prevention Study Group. Effect of a zoster vaccine on herpes zoster-related interference with functional status and health-related quality-of-life measures in older adults. J Am Geriatr Soc. 2010 Sep;58(9):1634-41. doi: 10.1111/j.1532-5415.2010.03021.x.
• Background Drolet M, Levin MJ, Schmader KE, Johnson R, Oxman MN, Patrick D, Fournier SO, Mansi JA, Brisson M. Employment related productivity loss associated with herpes zoster and postherpetic neuralgia: a 6-month prospective study. Vaccine. 2012 Mar 9;30(12):2047-50. doi: 10.1016/j.vaccine.2012.01.045. Epub 2012 Jan 28.

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