Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation
Catia T Perciani, Bashir Farah, Rupert Kaul, Mario A Ostrowski, Salaheddin M Mahmud, Omu Anzala, Walter Jaoko, KAVI-ICR Team, Kelly S MacDonald, Catia T Perciani, Bashir Farah, Rupert Kaul, Mario A Ostrowski, Salaheddin M Mahmud, Omu Anzala, Walter Jaoko, KAVI-ICR Team, Kelly S MacDonald
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.
Keywords: AIDS vaccine; AIDS/HIV; Cytokines; T cells; Vaccines.
Conflict of interest statement
Conflict of interest: SMM has received grants for unrelated studies from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer, and Roche-Assurex. SMM has received fees as an advisory board member for Sanofi Pasteur.
Figures
Source: PubMed