Peacey Matthew, Wilson Sarah, Perret Rachel, Ronchese Franca, Ward Vernon K, Young Vivienne, Young Sarah L, Baird Margaret A
Department of Microbiology and Immunology, School of Medical Sciences, University of Otago, 720 Cumberland Street, Dunedin, New Zealand.
Vaccine. 2008 Oct 3;26(42):5334-7. doi: 10.1016/j.vaccine.2008.07.074. Epub 2008 Aug 14.
Recombinant virus-like particles (VLP) expressing heterologous tumor antigens have recently been investigated for use as vaccines. We have chemically conjugated ovalbumin (OVA) or OVA-derived CD4 (OTII) and CD8 (OTI) epitopes, to rabbit hemorrhagic disease virus (RHDV) VLP. VLP conjugated with OVA were able to cross-prime CD8+ cells from OT1 mice transgenic for the OVA T cell receptor. VLP.OTI was able to induce higher antigen-specific cytotoxicity in vivo than VLP mixed with either the protein or the peptide. Furthermore we have shown that the growth of the aggressive B16.OVA melanoma in mice was significantly delayed in those animals that had been vaccinated with VLP.OVA or with VLP coupled with both OTI and OTII peptides prior to the introduction of the tumor. Neither VLP.OTI nor VLP.OTII alone were capable of inhibiting tumor growth. This work suggests that RHDV VLP offer a versatile scaffold for multiple vaccine epitopes, enabling cross-presentation of the antigen to elicit potent cell-mediated and anti-tumor responses.
表达异源肿瘤抗原的重组病毒样颗粒（VLP）最近被研究用作疫苗。我们已将卵清蛋白（OVA）或OVA衍生的CD4（OTII）和CD8（OTI）表位化学偶联到兔出血症病毒（RHDV）VLP上。与OVA偶联的VLP能够交叉激活来自表达OVA T细胞受体的OT1转基因小鼠的CD8 +细胞。VLP.OTI在体内比与蛋白质或肽混合的VLP诱导更高的抗原特异性细胞毒性。此外，我们已经表明，在接种肿瘤之前用VLP.OVA或与OTI和OTII肽偶联的VLP接种的小鼠中，侵袭性B16.OVA黑色素瘤的生长明显延迟。单独的VLP.OTI和VLP.OTII都不能抑制肿瘤生长。这项工作表明，RHDV VLP为多种疫苗表位提供了一个通用支架，能够交叉呈递抗原以引发有效的细胞介导和抗肿瘤反应。
