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Protocol of a randomised controlled trial characterising the immune responses induced by varicella-zoster virus (VZV) vaccination in healthy Kenyan women: setting the stage for a potential VZV-based HIV vaccine
  1. Catia T Perciani1,
  2. Walter Jaoko2,3,
  3. Sharon Walmsley4,
  4. Bashir Farah2,
  5. Salaheddin M Mahmud5,
  6. Mario Ostrowski1,6,
  7. Omu Anzala2,3,
  8. KAVI-ICR Team2,
  9. Kelly S MacDonald1,7
  1. 1 Department of Immunology, University of Toronto, Toronto, Ontario, Canada
  2. 2 Kenyan AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), Nairobi, Kenya
  3. 3 Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
  4. 4 Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
  5. 5 Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  6. 6 Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada
  7. 7 Section of Infectious Diseases, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  1. Correspondence to Dr Kelly S MacDonald; Kelly.MacDonald{at}umanitoba.ca

Abstract

Introduction A protective HIV vaccine would be expected to induce durable effector immune responses at the mucosa, restricting HIV infection at its portal of entry. We hypothesise that use of varicella-zoster virus (VZV) as an HIV delivery vector could generate sustained and robust tissue-based immunity against HIV antigens to provide long-term protection against HIV. Given that HIV uniquely targets immune-activated T cells, the development of human vaccines against HIV must also involve a specific examination of the safety of the vector. Thus, we aim to evaluate the effects of VZV vaccination on the recipients’ immune activation state, and on VZV-specific circulating humoral and cellular responses in addition to those at the cervical and rectal mucosa.

Methods and analysis This open-label, randomised, longitudinal crossover study includes healthy Kenyan VZV-seropositive women at low risk for HIV infection. Participants receive a single dose of a commercial live-attenuated VZVOka vaccine at either week 0 (n=22) or at week 12 (n=22) of the study and are followed for 48 and 36 weeks postvaccination, respectively. The primary outcome is the change on cervical CD4+ T-cell immune activation measured by the coexpression of CD38 and HLA-DR 12 weeks postvaccination compared with the baseline (prevaccination). Secondary analyses include postvaccination changes in VZV-specific mucosal and systemic humoral and cellular immune responses, changes in cytokine and chemokine measures, study acceptability and feasibility of mucosal sampling and a longitudinal assessment of the bacterial community composition of the mucosa.

Ethics and dissemination The study has ethical approval from Kenyatta National Hospital/University of Nairobi Ethics and Research Committee, the University of Toronto Research Ethics Board and by Kenyan Pharmacy and Poisons Board. Results will be presented at conferences, disseminated to participants and stakeholders as well as published in peer-reviewed journals.

Trial registration number NCT02514018. Pre-results.

  • varicella-zoster virus
  • HIV vaccine
  • immune activation
  • mucosal immunity
  • herpes zoster
  • herpesviridae infections
  • virus diseases

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Footnotes

  • Contributors KSM conceived the study. CTP, KSM, WJ, OA, BF, SW and MO initiated, designed and implemented the study. Members of the Kenyan AIDS Vaccine Initiative-Institute of Clinical Research were involved with the design and study implementation. SMM is responsible for the primary statistical analysis. All authors contributed to refinement of the study and approved the final manuscript.

  • Funding This study has been funded by the Canadian Institutes of Health Research (CIHR Team Grant—Research Operating THA:11960). CTP was supported by Vanier Canada Graduate Scholarship, The Delta Kappa Gamma Society World Fellowship and Ontario Graduate Scholarship. KSM was funded by an Ontario HIV Treatment Network Senior Investigator Award. KSM is currently supported by the HE Sellers Research Chair. SW is supported by a chair in clinical HIV management from the Ontario HIV treatment network. SMM is a Canada Research Chair in Pharmaco-epidemiology and Vaccine Evaluation.

  • Competing interests SMM has received grants for unrelated studies from GSK, Merck, Pfizer and Sanofi, and served on advisory boards for GSK and Pfizer.

  • Patient consent Obtained.

  • Ethics approval Kenyatta National Hospital/University of Nairobi Ethics and Research Committee, the University of Toronto Research Ethics Board and by Kenyan Pharmacy and Poisons Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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