Schwarz Benjamin, Morabito Kaitlyn M, Ruckwardt Tracy J, Patterson Dustin P, Avera John, Miettinen Heini M, Graham Barney S, Douglas Trevor
Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, United States.
ACS Biomater Sci Eng. 2016;2(12):2324-2332. doi: 10.1021/acsbiomaterials.6b00532. Epub 2016 Nov 3.
Subunit vaccines provide a safe, focused alternative to conventional vaccines. However, these vaccines often require significant adjuvants and are particularly hard to target toward cytotoxic T lymphocyte (CTL) immunity. Viruslike particles (VLPs) provide biomaterial scaffolds with pathogen-like polyvalent structures making them useful platforms for biomimetic antigen delivery to the immune system. Encapsidation of antigens within VLPs has been shown to enhance antigen availability for CD8 T cell responses. Here, we examine the potential to generate complex responses to multiple subunit antigens localized within the same VLP particle. Two proteins of respiratory syncytial virus (RSV) with well-characterized CD8 T cell responses, the matrix (M) and matrix 2 (M2) proteins, were successfully coencapsidated within the P22 VLP. Upon intranasal administration in mice, the particles stimulated CD8 T cell memory responses against both antigens. In addition, vaccination elicited tissue-resident T cell populations. Upon subsequent RSV challenge, P22-M/M2-treated mice displayed significantly reduced lung viral titers. This demonstrates the utility of the P22 VLP in directing immune responses to multiple encapsidated viral antigens, demonstrating the potential of this technology to facilitate immunity to multiple targets simultaneously.
亚单位疫苗为传统疫苗提供了一种安全、有针对性的替代方案。然而，这些疫苗通常需要大量佐剂，并且特别难以靶向细胞毒性T淋巴细胞（CTL）免疫。病毒样颗粒（VLP）提供了具有病原体样多价结构的生物材料支架，使其成为向免疫系统进行仿生抗原递送的有用平台。已证明将抗原包裹在VLP内可提高CD8 T细胞反应中抗原的可用性。在这里，我们研究了对位于同一VLP颗粒内的多种亚单位抗原产生复杂反应的潜力。呼吸道合胞病毒（RSV）的两种具有明确CD8 T细胞反应的蛋白质，即基质（M）蛋白和基质2（M2）蛋白，成功地共同包裹在P22 VLP内。在小鼠鼻内给药后，这些颗粒刺激了针对两种抗原的CD8 T细胞记忆反应。此外，疫苗接种引发了组织驻留T细胞群体。在随后的RSV攻击后，经P22-M/M2处理的小鼠的肺病毒滴度显著降低。这证明了P22 VLP在引导对多种包裹的病毒抗原的免疫反应中的效用，证明了该技术同时促进对多个靶标的免疫的潜力。
