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

Autor: Zacharia A; Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Harberts E; Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD, USA., Valencia SM; Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Myers B; Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Sanders C; Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Jain A; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS, USA., Larson NR; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS, USA., Middaugh CR; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS, USA., Picking WD; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS, USA., Difilippantonio S; Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Kirnbauer R; Laboratory of Viral Oncology (LVO), Department of Dermatology, Medical University of Vienna, Austria, EU., Roden RB; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA., Pinto LA; HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Shoemaker RH; Chemopreventive Agent Development Group, Division of Cancer Prevention, NCI, Bethesda, MD, USA., Ernst RK; Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD, USA., Marshall JD; Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. Electronic address: jason.marshall2@nih.gov.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2021 Jan 08; Vol. 39 (2), pp. 292-302. Date of Electronic Publication: 2020 Dec 10.
DOI: 10.1016/j.vaccine.2020.11.066
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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