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

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 5vectored (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.

Gardnerella subgroup dominant microbiomes are associated with divergent cervicovaginal immune responses in a longitudinal cohort of Kenyan women

“…This trial examined the safety and immunogenicity of the VZV Oka vaccine strain as a potential HIV vaccine vector (ClinicalTrials.gov: NCT02514018). As described by Perciani et al, VZV vaccination did not significantly alter the cervicovaginal immune responses examined in this ancillary study ( 18 ). Ethical approvals were granted by the Kenyatta National Hospital/University of Nairobi Ethics and Research Committee, the University of Toronto Research Board and the Kenyan Pharmacy and Poisons Board, with all participants providing informed consent.…”

“…Vaginal swabs were collected at each visit for the diagnosis of BV using the Nugent criteria (Nugent-BV) and VVC using microscopy as previously described ( 45 , 46 ). HSV-2 seropositivity was measured only at enrollment ( 18 ).…”

“…Cellular data processing was conducted using FlowJo (TreeStar Inc.). The gating strategy for the cellular markers used in this study has been previously published ( 18 , 52 ). Cellular samples were not acquired on week 36 of the study, and downstream analysis also excluded samples that did not pass the flow cytometer’s quality control cutoff.…”

“…To reduce the dimensionality of the cytokine dataset, principal component analysis (PCA) was performed using IBM SPSS Statistics (Version 23) as previously described ( 18 ). Briefly, sampling adequacy was measured by the Kaiser-Meyer-Olkin test, and Bartlett’s test of sphericity using all log10-normalized fourteen cytokine measurements collected throughout all the study visits.…”

Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids

“…VZV is the only human herpesvirus for which a licensed live attenuated vaccine, vOka, has been developed and widely administrated in several countries for decades 11 . VZV has also been used as an experimental vaccine vector against various pathogens 12 , including human immunodeficiency virus (HIV) [13][14][15][16] , and for the treatment of cancer 17,18 .…”