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Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation.

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Title: Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation.
Authors: Perciani CT; Department of Immunology, University of Toronto, Toronto, Ontario, Canada., Farah B; Kenyan AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), University of Nairobi, Nairobi, Kenya., Kaul R; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; University Health Network, Toronto, Ontario, Canada., Ostrowski MA; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; Keenan Research Center, St. Michael's Hospital, Toronto, Ontario, Canada., Mahmud SM; Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada., Anzala O; Kenyan AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), University of Nairobi, Nairobi, Kenya.; Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya., Jaoko W; Kenyan AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), University of Nairobi, Nairobi, Kenya.; Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya., MacDonald KS; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; Section of Infectious Diseases, Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.; Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Corporate Authors: KAVI-ICR Team
Source: The Journal of clinical investigation [J Clin Invest] 2019 Feb 01; Vol. 129 (2), pp. 875-886. Date of Electronic Publication: 2019 Jan 22.
Publication Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
Imprint Name(s): Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
MeSH Terms: AIDS Vaccines*/administration & dosage , AIDS Vaccines*/immunology , Herpesvirus 3, Human*/genetics , Herpesvirus 3, Human*/immunology , Virus Activation*/drug effects , Virus Activation*/immunology, CD4-Positive T-Lymphocytes/*immunology , HIV-1/*physiology, CD4-Positive T-Lymphocytes/pathology ; CD4-Positive T-Lymphocytes/virology ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology ; Varicella Zoster Virus Infection/immunology ; Varicella Zoster Virus Infection/pathology ; Varicella Zoster Virus Infection/prevention & control ; Adult ; Female ; Humans ; Kenya
Abstract: Background: Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA.
Methods: Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters.
Results: Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination.
Conclusion: This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine.
Trial Registration: ClinicalTrials.gov NCT02514018.
Funding: Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments.
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Grant Information: THA-11960 Canada CIHR
Contributed Indexing: Keywords: AIDS vaccine; AIDS/HIV; Cytokines; T cells; Vaccines
Molecular Sequence: ClinicalTrials.gov NCT02514018
Substance Nomenclature: 0 (AIDS Vaccines)
0 (Vaccines, Attenuated)
Entry Date(s): Date Created: 20181205 Date Completed: 20191216 Latest Revision: 20200309
Update Code: 20260130
PubMed Central ID: PMC6355215
DOI: 10.1172/JCI124473
PMID: 30511963
Database: MEDLINE
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Perciani+CT%22">Perciani CT</searchLink>; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.<br /><searchLink fieldCode="AU" term="%22Farah+B%22">Farah B</searchLink>; Kenyan AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), University of Nairobi, Nairobi, Kenya.<br /><searchLink fieldCode="AU" term="%22Kaul+R%22">Kaul R</searchLink>; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; University Health Network, Toronto, Ontario, Canada.<br /><searchLink fieldCode="AU" term="%22Ostrowski+MA%22">Ostrowski MA</searchLink>; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.; Keenan Research Center, St. Michael's Hospital, Toronto, Ontario, Canada.<br /><searchLink fieldCode="AU" term="%22Mahmud+SM%22">Mahmud SM</searchLink>; Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.<br /><searchLink fieldCode="AU" term="%22Anzala+O%22">Anzala O</searchLink>; Kenyan AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), University of Nairobi, Nairobi, Kenya.; Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.<br /><searchLink fieldCode="AU" term="%22Jaoko+W%22">Jaoko W</searchLink>; Kenyan AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), University of Nairobi, Nairobi, Kenya.; Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.<br /><searchLink fieldCode="AU" term="%22MacDonald+KS%22">MacDonald KS</searchLink>; Department of Immunology, University of Toronto, Toronto, Ontario, Canada.; Section of Infectious Diseases, Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.; Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
– Name: AuthorCorporate
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  Data: <searchLink fieldCode="CA" term="%22KAVI-ICR+Team%22">KAVI-ICR Team</searchLink>
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  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%227802877%22">The Journal of clinical investigation</searchLink> [J Clin Invest] 2019 Feb 01; Vol. 129 (2), pp. 875-886. <i>Date of Electronic Publication: </i>2019 Jan 22.
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  Data: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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  Data: English
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22American+Society+for+Clinical+Investigation%22">American Society for Clinical Investigation </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>7802877 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1558-8238 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2200219738%22">00219738 </searchLink><i>NLM ISO Abbreviation: </i>J Clin Invest <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: 1999- : Ann Arbor, MI : American Society for Clinical Investigation<br /><i>Original Publication</i>: New Haven [etc.] American Society for Clinical Investigation.
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22AIDS+Vaccines%22">AIDS Vaccines*</searchLink>/<searchLink fieldCode="MM" term="%22AIDS+Vaccines+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22AIDS+Vaccines%22">AIDS Vaccines*</searchLink>/<searchLink fieldCode="MM" term="%22AIDS+Vaccines+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Herpesvirus+3%2C+Human%22">Herpesvirus 3, Human*</searchLink>/<searchLink fieldCode="MM" term="%22Herpesvirus+3%2C+Human+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Herpesvirus+3%2C+Human%22">Herpesvirus 3, Human*</searchLink>/<searchLink fieldCode="MM" term="%22Herpesvirus+3%2C+Human+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Virus+Activation%22">Virus Activation*</searchLink>/<searchLink fieldCode="MM" term="%22Virus+Activation+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Virus+Activation%22">Virus Activation*</searchLink>/<searchLink fieldCode="MM" term="%22Virus+Activation+immunology%22">immunology</searchLink><br /><searchLink fieldCode="MM" term="%22CD4-Positive+T-Lymphocytes%22">CD4-Positive T-Lymphocytes</searchLink>/<searchLink fieldCode="MM" term="%22CD4-Positive+T-Lymphocytes+immunology%22">*immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22HIV-1%22">HIV-1</searchLink>/<searchLink fieldCode="MM" term="%22HIV-1+physiology%22">*physiology</searchLink><br /><searchLink fieldCode="MH" term="%22CD4-Positive+T-Lymphocytes%22">CD4-Positive T-Lymphocytes</searchLink>/<searchLink fieldCode="MH" term="%22CD4-Positive+T-Lymphocytes+pathology%22">pathology</searchLink> ; <searchLink fieldCode="MH" term="%22CD4-Positive+T-Lymphocytes%22">CD4-Positive T-Lymphocytes</searchLink>/<searchLink fieldCode="MH" term="%22CD4-Positive+T-Lymphocytes+virology%22">virology</searchLink> ; <searchLink fieldCode="MH" term="%22Vaccines%2C+Attenuated%22">Vaccines, Attenuated</searchLink>/<searchLink fieldCode="MH" term="%22Vaccines%2C+Attenuated+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Vaccines%2C+Attenuated%22">Vaccines, Attenuated</searchLink>/<searchLink fieldCode="MH" term="%22Vaccines%2C+Attenuated+immunology%22">immunology</searchLink> ; <searchLink fieldCode="MH" term="%22Varicella+Zoster+Virus+Infection%22">Varicella Zoster Virus Infection</searchLink>/<searchLink fieldCode="MH" term="%22Varicella+Zoster+Virus+Infection+immunology%22">immunology</searchLink> ; <searchLink fieldCode="MH" term="%22Varicella+Zoster+Virus+Infection%22">Varicella Zoster Virus Infection</searchLink>/<searchLink fieldCode="MH" term="%22Varicella+Zoster+Virus+Infection+pathology%22">pathology</searchLink> ; <searchLink fieldCode="MH" term="%22Varicella+Zoster+Virus+Infection%22">Varicella Zoster Virus Infection</searchLink>/<searchLink fieldCode="MH" term="%22Varicella+Zoster+Virus+Infection+prevention+%26+control%22">prevention & control</searchLink> ; <searchLink fieldCode="MH" term="%22Adult%22">Adult</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Kenya%22">Kenya</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA.<br />Methods: Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters.<br />Results: Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination.<br />Conclusion: This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine.<br />Trial Registration: ClinicalTrials.gov NCT02514018.<br />Funding: Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments.
– Name: Ref
  Label: References
  Group: RefInfo
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  Data: <i>Keywords: </i>AIDS vaccine; AIDS/HIV; Cytokines; T cells; Vaccines
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        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 875
    Subjects:
      – SubjectFull: CD4-Positive T-Lymphocytes pathology
        Type: general
      – SubjectFull: CD4-Positive T-Lymphocytes virology
        Type: general
      – SubjectFull: Vaccines, Attenuated administration & dosage
        Type: general
      – SubjectFull: Vaccines, Attenuated immunology
        Type: general
      – SubjectFull: Varicella Zoster Virus Infection immunology
        Type: general
      – SubjectFull: Varicella Zoster Virus Infection pathology
        Type: general
      – SubjectFull: Varicella Zoster Virus Infection prevention & control
        Type: general
      – SubjectFull: Adult
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Kenya
        Type: general
      – SubjectFull: AIDS Vaccines administration & dosage
        Type: general
      – SubjectFull: AIDS Vaccines immunology
        Type: general
      – SubjectFull: Herpesvirus 3, Human genetics
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      – SubjectFull: Herpesvirus 3, Human immunology
        Type: general
      – SubjectFull: Virus Activation drug effects
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      – SubjectFull: Virus Activation immunology
        Type: general
      – SubjectFull: CD4-Positive T-Lymphocytes immunology
        Type: general
      – SubjectFull: HIV-1 physiology
        Type: general
    Titles:
      – TitleFull: Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation.
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            – D: 01
              M: 02
              Text: 2019 Feb 01
              Type: published
              Y: 2019
          Identifiers:
            – Type: issn-electronic
              Value: 1558-8238
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              Value: 129
            – Type: issue
              Value: 2
          Titles:
            – TitleFull: The Journal of clinical investigation
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