Live Attenuated Zoster Vaccine Boosts Varicella Zoster Virus (VZV)–Specific Humoral Responses Systemically and at the Cervicovaginal Mucosa of Kenyan VZV-Seropositive Women

The Journal of Infectious Diseases MAJOR ARTICLE Live Attenuated Zoster Vaccine Boosts Varicella Zoster Virus (VZV)–Specific Humoral Responses Systemically and at the Cervicovaginal Mucosa of Kenyan VZV-Seropositive Women Catia T. Perciani,1 Manmeet Sekhon,1 Sabrina Hundal,1 Bashir Farah,2 Mario A. Ostrowski,1,3 A. Omu Anzala,2,4 Lyle R. McKinnon,4,5,6 Walter Jaoko,2,4 and Kelly S. MacDonald1,7; for the Institute of Tropical and Infectious Diseases (UNITID) Group and the Kenyan AIDS Vaccine Initiative–Institute of Clinical Research (KAVI-ICR) Teama Background. Attenuated varicella zoster virus (VZV) is a promising vector for recombinant vaccines. Because human immunodeficiencyvirus (HIV) vaccines are believed to require mucosal immunogenicity, we characterized mucosal VZV-specific humoral immunity following VZVOka vaccination. Methods. Adult Kenyan VZV-seropositive women (n = 44) received a single dose of the live zoster VZVOka vaccine. The anamnestic responses to the virus were followed longitudinally in both plasma and mucosal secretions using an in-house glycoprotein enzyme-linked immunosorbent assay and safety and reactogenicity monitored. VZV seroprevalence and baseline responses to the virus were also characterized in our cohorts (n = 288). Results. Besides boosting anti-VZV antibody responses systemically, vaccination also boosted anti-VZV immunity in the cervicovaginal mucosa with a 2.9-fold rise in immunoglobulin G (P < .0001) and 1.6-fold rise in immunoglobulin A (IgA) (P = .004) from the time before immunization and 4 weeks postvaccination. Baseline analysis demonstrated high avidity antibodies at the gastrointestinal and genital mucosa of VZV-seropositive women. Measurement of VZV-specific IgA in saliva is a sensitive tool for detecting prior VZV infection. Conclusions. VZVOka vaccine was safe and immunogenic in VZV-seropositive adult Kenyan women. We provided compelling evidence of VZV ability to induce genital mucosa immunity. Clinical Trials Registration. NCT02514018. Keywords. varicella zoster virus; zoster vaccine; mucosal immunity; vaccine vector; HIV/AIDS vaccine. Varicella zoster virus (VZV) is a member of the Herpesviridae family and the causative agent of varicella (chickenpox) and herpes zoster (HZ; shingles). Exposure to VZV often results in productive infection in individuals without preexisting immunity to the virus. Unlike varicella, which occurs mainly during childhood [1], secondary reactivation disease with VZV (HZ) occurs mainly in older adults and immunocompromised individuals as a consequence of waning VZV-specific cellular Received 24 April 2018; editorial decision 21 May 2018; accepted 23 May 2018; published online May 25, 2018 aMembers of the UNITID Group and the KAVI-ICR Team are listed in the Notes. Correspondence: K. S. MacDonald, MD, FRCPC, Max Rady College of Medicine, University of Manitoba, Office Rm 501, Basic Medical Sciences Building, 745 Bannatyne Ave, Winnipeg, MB R3E0J9, Canada (). The Journal of Infectious Diseases®  2018;218:1210–8 © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact DOI: 10.1093/infdis/jiy320 1210 • JID 2018:218 (15 October) • Perciani et al immunity [2, 3]. Live attenuated VZV vaccines available for the prevention of varicella and HZ have been shown to be safe and effective in preventing both diseases [4–9]. Most recently, a recombinant glycoprotein E–based HZ vaccine combined with a novel adjuvant has demonstrated promise in elderly patients [10], although this approach has not been used to prevent varicella. While recombinant protein vaccines typically require periodic booster doses as the only means to boost immunity, live attenuated vaccines such as the Oka strain VZV (VZVOka) can establish latency in human neural ganglia and the autonomic nerve ganglia found in the basal layer of the enteric mucosa similarly to the wild-type VZV [11, 12]. It has been proposed that periodic VZV subclinical reactivation boosts the humoral and cellular immune responses against the virus, thus providing long-lived protection. The well-established record of safety and immunogenicity of attenuated, replication-competent VZVOka vaccine in preventing varicella and HZ, combined with intrinsic viral features, has raised interest in using VZVOka as a platform for the expression of foreign 1Department of Immunology, University of Toronto, Ontario, Canada; 2Kenyan AIDS Vaccine Initiative–Institute of Clinical Research, Nairobi, Kenya; 3Keenan Research Centre for Biomedical Science of St Michael’s Hospital, Toronto, Ontario, Canada; 4Department of Medical Microbiology, University of Nairobi, Kenya; 5Department of Medical Microbiology and Infectious Diseases, Rady College of Medicine, University of Manitoba, Winnipeg, Canada; 6Centre for the AIDS Programme of Research in South Africa, Durban; and 7Section of Infectious Diseases, Department of Internal Medicine, Rady College of Medicine, University of Manitoba, Winnipeg, Canada MATERIALS AND METHODS Study Design The Kenyan AIDS Vaccine Initiative (KAVI)–VZV-001 study design, including eligibility criteria, study outcomes, immunization schedule, timeline, and sample collection are detailed in the study protocol by Perciani et al [14]. In brief, 44 healthy Kenyan women with a median age of 26 years (interquartile range, 21.5–30.5 years), seropositive for VZV, seronegative for HIV types 1 and 2, and at low risk for HIV infection were enrolled in the study. Upon enrollment, the subjects were randomly assigned (1:1) to an immediate group that received the vaccine right after baseline sample collection or into a delayed group that received the vaccine 12 weeks postenrollment, after undergoing baseline sampling collection a total of 4 times prior to immunization [14]. All subjects were determined to be not pregnant prior to vaccination and agreed to use an effective contraceptive method during the study duration. Participants were followed for 36–48 weeks postimmunization depending on the group they were assigned to. The quantification of VZV-specific antibodies (Abs) prior to and after vaccination was performed in plasma, cervicovaginal secretions, saliva, and rectal secretions as previously described [14]. All participants included in this study provided written informed consent. KAVI-VZV-001 is registered with ClinicalTrials.gov (NCT02514018) and was approved by Kenyatta National Hospital/University of Nairobi (KNH/UON), Ethics and Research Committee (ERC), the University of Toronto Research Ethics Board (REB), a (...truncated)