Bidart J, Mignaqui A, Kornuta C, Lupi G, Gammella M, Soria I, Galarza R, Ferella A, Cardillo S, Langellotti C, Quattrocchi V, Durocher Y, Wigdorovitz A, Marcipar I, Zamorano P
Instituto de Virología e Innovaciones Tecnológicas-IVIT, CICVyA, INTA-CONICET, Hurlingham, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Instituto de Investigaciones Forestales y Agropecuarias Bariloche, IFAB, INTA - CONICET, San Carlos de Bariloche, Rio Negro, Argentina.
Virus Res. 2021 May;297:198339. doi: 10.1016/j.virusres.2021.198339. Epub 2021 Feb 14.
Foot and Mouth Disease Virus (FMDV) causes economy losses and is controlled by vaccination in many countries. Vaccine formulations based on empty capsids or Virus-Like Particles (VLPs) have the advantage of avoiding the biological hazard of using infectious FMDV, albeit are poorly immunogenic. Recently, we have described that ISPA a new Immune Stimulating Complex adjuvant, is useful to improve the response against FMD of vaccines that use inactivated virus. Now, the adjuvant effects of ISPA and ISA 206 (water/oil/water) on a VLPs-based FMD vaccine were evaluated. VLPs (strain A/Argentina/2001) were obtained in mammalian cell cultures and their elicitation of an immune response against FMDV with and without ISPA or ISA 206 was evaluated in mice as a first approach. Notably, VLPs-ISPA and VLPs-ISA 206 vaccines induced protection against viral challenge in 100 % of mice, while protection induced by VLPs alone was of 40 %. Total and neutralizing FMDV antibodies were higher in the VLPs-ISPA and VLPs-ISA 206 groups compared to the VLPs group. VLPs-ISPA induced significantly higher (p < 0.001) IgG1, IgG2a, IgG2b and IgG3 titers than the VLPs vaccine. Moreover, in comparison with non-adjuvanted VLPs, VLPs-ISPA and VLPs-ISA 206 elicited an increased virus-specific T response, including higher IFNγ+/CD8 + lymphocyte production in mice. When these vaccines were tested in calves, antibody titers reached an Expected Percentage of Protection (EPP) above 90 % in the case of the VLPs-ISPA and VLPs-ISA 206 vaccines, while, in the VLPs group, EPP reached 25 %. IFNγ levels secreted by mononuclear cells of VLP-ISPA-vaccinated cattle were significantly higher than in the VLPs group. Overall, the results demonstrate that VLPs-ISPA or VLPs-ISA 206 are promising formulations for the development of a novel FMD vaccine.
口蹄疫病毒（FMDV）会造成经济损失，在许多国家通过接种疫苗来进行控制。基于空衣壳或病毒样颗粒（VLPs）的疫苗制剂具有避免使用传染性FMDV带来生物危害的优势，尽管其免疫原性较差。最近，我们描述了一种新型免疫刺激复合物佐剂ISPA，它有助于提高使用灭活病毒的口蹄疫疫苗的免疫反应。现在，评估了ISPA和ISA 206（水/油/水）对基于VLPs的口蹄疫疫苗的佐剂效果。VLPs（A/阿根廷/2001株）在哺乳动物细胞培养物中获得，作为第一步，在小鼠中评估了它们在有或没有ISPA或ISA 206的情况下引发针对FMDV的免疫反应。值得注意的是，VLPs - ISPA和VLPs - ISA 206疫苗在100%的小鼠中诱导了针对病毒攻击的保护作用，而仅VLPs诱导的保护率为40%。与VLPs组相比，VLPs - ISPA和VLPs - ISA 206组中的口蹄疫病毒总抗体和中和抗体更高。VLPs - ISPA诱导的IgG1、IgG2a、IgG2b和IgG3滴度显著高于VLPs疫苗（p < 0.001）。此外，与未加佐剂的VLPs相比，VLPs - ISPA和VLPs - ISA 206引发了增强的病毒特异性T反应，包括小鼠中更高的IFNγ + / CD8 +淋巴细胞产生。当在小牛中测试这些疫苗时，对于VLPs - ISPA和VLPs - ISA 206疫苗，抗体滴度达到了90%以上的预期保护百分比（EPP），而在VLPs组中，EPP达到了25%。接种VLP - ISPA的牛的单核细胞分泌的IFNγ水平显著高于VLPs组。总体而言，结果表明VLPs - ISPA或VLPs - ISA 206是开发新型口蹄疫疫苗的有前景的制剂。
