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    Optimization of RG1-VLP vaccine performance in mice with novel TLR4 agonists

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    Author
    Zacharia, Athina
    Harberts, Erin
    Valencia, Sarah M
    Myers, Breana
    Sanders, Chelsea
    Jain, Akshay
    Larson, Nicholas R
    Middaugh, C Russell
    Picking, William D
    Difilippantonio, Simone
    Kirnbauer, Reinhard
    Roden, Richard B
    Pinto, Ligia A
    Shoemaker, Robert H
    Ernst, Robert K
    Marshall, Jason D
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    Date
    2020-12-10
    Journal
    Vaccine
    Publisher
    Elsevier Ltd.
    Type
    Article
    
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    See at
    https://doi.org/10.1016/j.vaccine.2020.11.066
    Abstract
    Current human papilloma virus (HPV) vaccines provide substantial protection against the most common HPV types responsible for oral and anogenital cancers, but many circulating cancer-causing types remain that lack vaccine coverage. The novel RG1-VLP (virus-like particle) vaccine candidate utilizes the HPV16-L1 subunit as a backbone to display an inserted HPV16-L2 17–36 a.a. “RG1” epitope; the L2 RG1 epitope is conserved across many HPV types and the generation of cross-neutralizing antibodies (Abs) against which has been demonstrated. In an effort to heighten the immunogenicity of the RG1-VLP vaccine, we compared in BALB/c mice adjuvant formulations consisting of novel bacterial enzymatic combinatorial chemistry (BECC)-derived toll-like receptor 4 (TLR4) agonists and the aluminum hydroxide adjuvant Alhydrogel. In the presence of BECC molecules, consistent improvements in the magnitude of Ab responses to both HPV16-L1 and the L2 RG1 epitope were observed compared to Alhydrogel alone. Furthermore, neutralizing titers to HPV16 as well as cross-neutralization of pseudovirion (PsV) types HPV18 and HPV39 were augmented in the presence of BECC agonists as well. Levels of L1 and L2-specific Abs were achieved after two vaccinations with BECC/Alhydrogel adjuvant that were equivalent to or greater than levels achieved with 3 vaccinations with Alhydrogel alone, indicating that the presence of BECC molecules resulted in accelerated immune responses that could allow for a decreased dose schedule for VLP-based HPV vaccines. In addition, dose-sparing studies indicated that adjuvantation with BECC/Alhydrogel allowed for a 75% reduction in antigen dose while still retaining equivalent magnitudes of responses to the full VLP dose with Alhydrogel. These data suggest that adjuvant optimization of HPV VLP-based vaccines can lead to rapid immunity requiring fewer boosts, dose-sparing of VLPs expensive to produce, and the establishment of a longer-lasting humoral immunity.
    Rights/Terms
    Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Keyword
    Adjuvants
    HPV
    HPV-L2
    Human papillomavirus
    Neutralizing antibody
    Prophylactic vaccine
    TLR4
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14329
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.vaccine.2020.11.066
    Scopus Count
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    UMB Open Access Articles 2020

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