Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston 77555, TX, USA.
Departments of Immunology/Microbiology and Internal Medicine, Rush University Cancer Center, Developmental Center for AIDS Research, Rush University Medical Center, Chicago 60612, IL, USA.
Vaccine. 2014 Feb 26;32(10):1174-80. doi: 10.1016/j.vaccine.2013.11.047. Epub 2013 Dec 2.
Vaccines that elicit robust CD8⁺ T cell responses are desirable for protection against infectious diseases and cancers. However, most vaccine adjuvants fail to elicit robust CD8⁺ T cell responses without inflammation and associated toxicity. We recently reported that self-assembling peptides that form nanofibers in physiological buffers elicited strong adjuvant-free and antigen-specific antibody responses in mice. However, whether or not such nanofibers likewise can elicit strong CD8⁺ T cell responses is unknown. Here, we demonstrate that the self-assembling peptide Q11 conjugated to a CD8⁺ T cell epitope of ovalbumin (Q11-OVA), elicits strong antigen-specific primary and recall responses, and in a vaccination regimen protects against subsequent infection. Importantly, we show that these antigenic peptide nanofibers do not persist as an inflammatory antigen depot at the injection site. Our results demonstrate for the first time that self-assembling peptides may be useful as carriers for vaccines where CD8⁺ T cell-mediated protection is needed.
能够引发强烈 CD8+T 细胞反应的疫苗是预防传染病和癌症的理想选择。然而,大多数疫苗佐剂在没有炎症和相关毒性的情况下无法引发强烈的 CD8+T 细胞反应。我们最近报道称,在生理缓冲液中自组装形成纳米纤维的肽能够在小鼠中引发强烈的无佐剂和抗原特异性抗体反应。然而,这种纳米纤维是否同样能够引发强烈的 CD8+T 细胞反应尚不清楚。在这里,我们证明了与卵清蛋白(Q11-OVA)的 CD8+T 细胞表位偶联的自组装肽 Q11 能够引发强烈的抗原特异性初次和回忆反应,并在疫苗接种方案中能够预防随后的感染。重要的是,我们表明这些抗原肽纳米纤维不会作为炎症性抗原库在注射部位持续存在。我们的研究结果首次表明,自组装肽可用作需要 CD8+T 细胞介导保护的疫苗的载体。
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