Adenovirus vectors as HIV-1 vaccines

D’Souza, M. Patricia; Yang, Otto O.

doi:10.1097/qad.0000000000000548

Cited by 9 publications

(8 citation statements)

References 53 publications

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“…The use of persistent replicating viral vectors could be instrumental in safely mimicking attenuated HIV antigenic presentation and helping mature and maintain a protective response via vaccine, as suggested by studies in NHP models using CMV as a vector for SIV genes (23)(24)(25). However, a detailed assessment of the mucosal immune responses induced by these viral vectors, including IA, is warranted if they are to be used as a chimeric vector bearing HIV antigens (26,27). Additionally, it has been shown that an activated immune microenvironment prior to vaccination can HIV coreceptor CCR5, the activation markers CD69 and Ki-67, and markers of cell migration and retention (α 4 β 7 , α 4 β 1 , α E β 7 ) in blood, cervix, and rectum.…”

Section: Introductionmentioning

confidence: 99%

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

Perciani

Farah

Kaul

et al. 2019

Journal of Clinical Investigation

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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.

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Section: Introductionmentioning

confidence: 99%

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

Perciani

Farah

Kaul

et al. 2019

Journal of Clinical Investigation

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“…There is reasonable consensus that both humoral and T-cell responses will be required for an effective HIV vaccine [1][2][3][4] and vaccine candidates designed to elicit these responses have undergone efficacy trials. Two trials (Step/Phambili) tested an adenovirus serotype-5 (Ad5) vector encoding HIV-1 Gag/Pol/Nef (MRKAd5 HIV-1) designed to induce T-cells to reduce viremia [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+ T cells with limited breadth of HIV-1 inhibition

Hayes

Cox

Coleman

et al. 2016

Aids

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“…119 Therefore, concern regarding preexisting vector immunity prompted the development of other Ad vectors with lower seroprevalence, including Ad26 and Ad35. 120,121 Ad26 and Ad35 studies have shown potential in phase I/II human vaccine trials. [122][123][124][125] A recent randomized, double-blind, placebo-controlled trial in 218 healthy adults using Ad26.…”

Section: New Vectorsmentioning

confidence: 99%