Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation.
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Date
2019-02-01Author
Perciani, CT
Farah, B
Kaul, R
Ostrowski, MA
Mahmud, SM
Anzala, O
Jaoko, W
KAVI-ICR Team
MacDonald, KS
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
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.
Citation
J Clin Invest. 2019 Feb 1;129(2):875-886Publisher
BMC
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- Faculty of Health Sciences (FHS) [10377]