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dc.contributor.authorZacharia, Athina
dc.contributor.authorHarberts, Erin
dc.contributor.authorValencia, Sarah M
dc.contributor.authorMyers, Breana
dc.contributor.authorSanders, Chelsea
dc.contributor.authorJain, Akshay
dc.contributor.authorLarson, Nicholas R
dc.contributor.authorMiddaugh, C Russell
dc.contributor.authorPicking, William D
dc.contributor.authorDifilippantonio, Simone
dc.contributor.authorKirnbauer, Reinhard
dc.contributor.authorRoden, Richard B
dc.contributor.authorPinto, Ligia A
dc.contributor.authorShoemaker, Robert H
dc.contributor.authorErnst, Robert K
dc.contributor.authorMarshall, Jason D
dc.date.accessioned2021-01-11T20:42:47Z
dc.date.available2021-01-11T20:42:47Z
dc.date.issued2020-12-10
dc.identifier.urihttp://hdl.handle.net/10713/14329
dc.description.abstractCurrent 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.en_US
dc.description.urihttps://doi.org/10.1016/j.vaccine.2020.11.066en_US
dc.language.isoenen_US
dc.publisherElsevier Ltd.en_US
dc.relation.ispartofVaccineen_US
dc.rightsCopyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.en_US
dc.subjectAdjuvantsen_US
dc.subjectHPVen_US
dc.subjectHPV-L2en_US
dc.subjectHuman papillomavirusen_US
dc.subjectNeutralizing antibodyen_US
dc.subjectProphylactic vaccineen_US
dc.subjectTLR4en_US
dc.titleOptimization of RG1-VLP vaccine performance in mice with novel TLR4 agonistsen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.vaccine.2020.11.066
dc.identifier.pmid33309485
dc.source.volume39
dc.source.issue2
dc.source.beginpage292
dc.source.endpage302
dc.source.countryUnited States
dc.source.countryNetherlands


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