4.5 Article

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

期刊

VACCINE
卷 39, 期 2, 页码 292-302

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2020.11.066

关键词

Human papillomavirus; HPV; Prophylactic vaccine; TLR4; Adjuvants; HPV-L2; Neutralizing antibody

资金

  1. National Cancer Institute, National Institutes of Health [HHSN261200800001E, HHSN272201800043C]

向作者/读者索取更多资源

The study demonstrated that utilizing novel BECC/Alhydrogel adjuvants can enhance the immunogenicity of HPV vaccines against multiple HPV types, promote the generation of cross-neutralizing antibodies, reduce the number of vaccinations needed, spare vaccine doses, accelerate immune responses, and establish longer-lasting humoral immunity.
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. (C) 2020 The Authors. Published by Elsevier Ltd.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据