The re-activating nature of Varicella Zoster Virus (VZV) may allow life long boosting when used as a vaccine vector in conjunction with HIV to generate durable immunity systemically and at the mucosa. This study aims to characterize mucosal immunity before and after vaccination with a commercial live-attenuated varicella-zoster virus vaccine with respect to immune activation state, mucosal homing properties and VZV-specific effector immune responses in healthy women at low risk for HIV acquisition.
An ideal HIV vaccine should be able to induce an effector specific immune response at the mucosal site which serves as the portal of HIV entry. The use of a persistent replicating viral vector such as Varicella-Zoster Virus (VZV) has great potential to assemble this specific response. Live-attenuated varicella-zoster virus has been used as a vaccine worldwide for over 25 years and has a well-described safety profile. However, its immunogenicity data in the African population are lacking. The general objective of this study will be to measure the magnitude and kinetics of the effector immune response and immune activation induced by live-attenuated varicella-zoster virus vaccine in a population of Kenyan women. Specifically, the study will measure immune activation in both cervical and rectal mucosae in the context of VZV-effector responses after vaccination and compare the observed immune activation in mucosal tissues and in blood. A total of 44 healthy women in Nairobi, aged 18-50 years will be recruited into the study, after obtaining their written informed consent. Eligibility to participate in the study will depend on results of laboratory tests, review of medical history, physical examination and answers to questions about HIV risk behaviours. The study will assess immune responses to both immediate and delayed administration of live-attenuated virus varicella-zoster vaccine in VZV-seropositive individuals. Participants will be randomly divided into 2 groups. Group 1 will receive a single dose of the vaccine at day 0 and Group 2 at day 84. The participants will be followed for a period of 9-12 months after receiving the vaccine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Commercial vaccine used to prevent shingles
KAVI-ICR, University of Nairobi
Nairobi, Kenya
Change in the median frequency of cervical CD38+HLA-DR+CD4+T cells after VZV-vaccination as a measure of immune activation
Comparison of the change in the median (Interquartile range - IQR) frequency of cervical CD38+HLA-DR+CD4+T cells between 1) Baseline and 3 months after (for the delayed group), and 2) Before and after 3 months of VZV vaccination (immediate and delayed groups).
Time frame: 3 months after VZV-vaccination
Composite measures of immune activation observed in mucosal tissues
Comparison of the change in the median (IQR) expression of activation markers such as CD38, CD69, Ki67 and HLA-DR in mucosal T cells (CD4+ and CD8+ T cells) between 1) Baseline and 3 months after (for the delayed group), and 2) Before and after 3 months of VZV vaccination (immediate and delayed groups)
Time frame: 3 months after VZV-vaccination
Composite measures of mucosal homing marker and HIV co-receptors observed in mucosal tissues
Comparison of the change in the median (IQR) expression of α4β7 and CCR5 in mucosal CD4+T cells between 1) Baseline and 3 months after (for the delayed group), and 2) Before and after 3 months of VZV vaccination (immediate and delayed groups)
Time frame: 3 months after VZV-vaccination
Mucosal level of inflammation (including IL-1β, IL-6 and IL8)
Time frame: 3 months after VZV-vaccination
Composite measures of immune activation observed in blood
Comparison of the change in the median (IQR) expression activation markers such as CD38, CD69, Ki67 and HLA-DR in systemic T cells (CD4+ and CD8+ T cells) between 1) Baseline and 3 months after (for the delayed group), and 2) Before and after 3 months of VZV vaccination (immediate and delayed groups)
Time frame: 3 months after VZV-vaccination
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Enrollment
45
Composite measures of mucosal homing marker and HIV co-receptors observed in blood
Comparison of the change in the median (IQR) expression of α4β7 and CCR5 in systemic CD4+T cells between 1) Baseline and 3 months after (for the delayed group), and 2) Before and after 3 months of VZV vaccination (immediate and delayed groups).
Time frame: 3 months after VZV-vaccination
Plasma level of inflammation (including IL-1β, IL-6 and IL8)
Time frame: 3 months after VZV-vaccination
Frequency and function of mucosal VZV-specific immune cells (including CD8+ and CD4+ T cell subsets)
Time frame: Longidudinally througout the study (up to 12 months)
Concentration of mucosal VZV-specific antibodies (IgG and IgA)
Time frame: Longidudinally througout the study (up to 12 months)
Frequency and function of systemic VZV-specific immune cells (including CD8+ and CD4+ T cell subsets)
Time frame: Longidudinally througout the study (up to 12 months)
Concentration of systemic VZV-specific antibodies (IgG and IgA)
Time frame: Longidudinally througout the study (up to 12 months)