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Setting the Stage for a Potential Va...
~
Perciani, Catia Taniela.
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Setting the Stage for a Potential Varicella-Zoster Virus (VZV)-Based HIV Vaccine: Characterization of the Mucosal Immune Response Induced by VZV Vaccination in Humans.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Setting the Stage for a Potential Varicella-Zoster Virus (VZV)-Based HIV Vaccine: Characterization of the Mucosal Immune Response Induced by VZV Vaccination in Humans./
Author:
Perciani, Catia Taniela.
Published:
Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:
331 p.
Notes:
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Contained By:
Dissertations Abstracts International81-04B.
Subject:
Immunology. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10974455
ISBN:
9781085755696
Setting the Stage for a Potential Varicella-Zoster Virus (VZV)-Based HIV Vaccine: Characterization of the Mucosal Immune Response Induced by VZV Vaccination in Humans.
Perciani, Catia Taniela.
Setting the Stage for a Potential Varicella-Zoster Virus (VZV)-Based HIV Vaccine: Characterization of the Mucosal Immune Response Induced by VZV Vaccination in Humans.
- Ann Arbor : ProQuest Dissertations & Theses, 2019 - 331 p.
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Thesis (Ph.D.)--University of Toronto (Canada), 2019.
This item must not be sold to any third party vendors.
In the face of enormous "Treatment as Prevention" efforts, we are still faced with new HIV infections every year. In 2017 alone, there were 1.8 million new HIV infections worldwide; experts feel we will never eliminate HIV in the absence of a vaccine. Among the vaccine strategies tested to date, those involving replicating recombinant viral vectors show the most promise. However, results obtained with multiple human adenovirus-vectored HIV vaccines raised concerns about the impact of pre-existing immunity boosted by the vector backbone on the safety and efficacy of an HIV vaccine. Studies in both human and non-human primates demonstrated that a protective HIV vaccine would most likely have to induce and sustain immunity at the genital and rectal mucosa, the portal of entry of HIV, without fueling disproportionate local inflammation. Varicella-zoster virus (VZV), the causative agent of chickenpox, holds several advantages as a vaccine vector such as its long-standing record of safety and immunogenicity in humans and its ability to maintain long-term immunity. However, the mucosal immune response induced by live-attenuated VZV vaccination remains unknown. I conducted a primary human clinical trial in a cohort of healthy VZV- seropositive Kenyan women (n=45) to assess this response. The immune activation status and VZV-specific immune responses were characterized longitudinally in systemic and mucosal specimens, including cervical cytobrushes and rectal biopsies, pre- and post-vaccination with the commercial live-attenuated VZVOka vaccine. Our data revealed that vaccination with VZV significantly boosted VZV-specific antibody responses in blood and in the female genital tract. Importantly, VZV vaccination did not increase the frequency of activated CD4 T cells or CD4 T cells expressing the HIV co- receptor CCR5 in blood, cervix or rectum. Additionally, there was no significant vaccine- induced change in the concentration of the pro-inflammatory cytokines in either cervico- vaginal or rectal secretions. These results support the downstream development and evaluation of a VZV-vectored chimeric HIV vaccine.
ISBN: 9781085755696Subjects--Topical Terms:
611031
Immunology.
Subjects--Index Terms:
Clinical trial
Setting the Stage for a Potential Varicella-Zoster Virus (VZV)-Based HIV Vaccine: Characterization of the Mucosal Immune Response Induced by VZV Vaccination in Humans.
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In the face of enormous "Treatment as Prevention" efforts, we are still faced with new HIV infections every year. In 2017 alone, there were 1.8 million new HIV infections worldwide; experts feel we will never eliminate HIV in the absence of a vaccine. Among the vaccine strategies tested to date, those involving replicating recombinant viral vectors show the most promise. However, results obtained with multiple human adenovirus-vectored HIV vaccines raised concerns about the impact of pre-existing immunity boosted by the vector backbone on the safety and efficacy of an HIV vaccine. Studies in both human and non-human primates demonstrated that a protective HIV vaccine would most likely have to induce and sustain immunity at the genital and rectal mucosa, the portal of entry of HIV, without fueling disproportionate local inflammation. Varicella-zoster virus (VZV), the causative agent of chickenpox, holds several advantages as a vaccine vector such as its long-standing record of safety and immunogenicity in humans and its ability to maintain long-term immunity. However, the mucosal immune response induced by live-attenuated VZV vaccination remains unknown. I conducted a primary human clinical trial in a cohort of healthy VZV- seropositive Kenyan women (n=45) to assess this response. The immune activation status and VZV-specific immune responses were characterized longitudinally in systemic and mucosal specimens, including cervical cytobrushes and rectal biopsies, pre- and post-vaccination with the commercial live-attenuated VZVOka vaccine. Our data revealed that vaccination with VZV significantly boosted VZV-specific antibody responses in blood and in the female genital tract. Importantly, VZV vaccination did not increase the frequency of activated CD4 T cells or CD4 T cells expressing the HIV co- receptor CCR5 in blood, cervix or rectum. Additionally, there was no significant vaccine- induced change in the concentration of the pro-inflammatory cytokines in either cervico- vaginal or rectal secretions. These results support the downstream development and evaluation of a VZV-vectored chimeric HIV vaccine.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10974455
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