Postgraduate Programme in Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Rua Gen, Gustavo Cordeiro de Farias, 384, 59012-570 Natal, Brazil; Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Rua Gen, Gustavo Cordeiro de Farias, 384, 59012-570 Natal, Brazil.
Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua da Juqueira, 100, 1800-166 Lisbon, Portugal.
Vaccine. 2021 Jul 30;39(33):4723-4732. doi: 10.1016/j.vaccine.2021.05.039. Epub 2021 May 27.
The infection caused by the protozoan Trypanosoma cruzi affects humans and is called as Chagas disease. Currently, the main measures available to reduce the incidence of this disease are drug treatment and vector control. Traditionally, the development of vaccines occurs mainly through the use of antigenic candidates of the etiologic agent in the form of a vaccine preparation. Virus-like particles (VLPs) are structures analogous to viral capsids composed essentially of structural proteins and are widely used in vaccination protocols because of their immunostimulatory properties. In this context, the objective of this study was to use strategies in a murine immunization model to characterize the immunostimulatory capacity of VLPs from Triatoma virus (TrV-VLPs), analysed in the presence or absence of the aluminium vaccine adjuvant. In parallel, to characterize the immunogenic behaviour of four T. cruzi chimeric recombinant proteins (mix-IBMP) associated with TrV-VLPs or aluminium vaccine adjuvant.
We immunized BALB/c mice once or twice, depending on the strategy, and collected serum samples at 15, 30 and 45 days after the immunization. Subsequently, serum samples from animals immunized with TrV-VLPs were used to determine total IgG, IgG1, IgG2a, IgG2b and IgG3 anti-TrV-VLPs by enzyme-linked immunosorbent assay (ELISA).
Data obtained demonstrate the ability of TrV-VLPs to preferably induce IgG2b and IgG3 type antibodies in the absence of aluminium adjuvant. In fact, the use of aluminium did not interfere with the total IgG profile of anti-TrV-VLPs. Interestingly, mix-IBMP had a better profile of total IgG, IgG1 and IgG3 subclasses when mixed with TrV-VLPs.
In conclusion, these results suggest the potential of TrV-VLPs as a vaccine adjuvant and the use of T. cruzi chimeric antigens as a rational strategy for the development of vaccines against the experimental model of Chagas disease.
原生动物克氏锥虫引起的感染会影响人类，被称为恰加斯病。目前，减少这种疾病发病率的主要措施是药物治疗和病媒控制。传统上，疫苗的开发主要通过使用病原体的抗原候选物作为疫苗制剂。病毒样颗粒（VLPs）是与病毒衣壳类似的结构，主要由结构蛋白组成，由于其免疫刺激特性，被广泛用于疫苗接种方案。在这种情况下，本研究的目的是使用小鼠免疫模型中的策略来表征 Triatoma 病毒（TrV-VLPs）的免疫刺激能力，分析时存在或不存在铝疫苗佐剂。同时，表征与 TrV-VLPs 或铝疫苗佐剂相关的四种 T. cruzi 嵌合重组蛋白（mix-IBMP）的免疫原性行为。
我们根据策略对 BALB/c 小鼠进行一次或两次免疫，并在免疫后 15、30 和 45 天收集血清样本。随后，使用来自用 TrV-VLPs 免疫的动物的血清样本通过酶联免疫吸附测定（ELISA）来确定针对 TrV-VLPs 的总 IgG、IgG1、IgG2a、IgG2b 和 IgG3。
获得的数据表明，在没有铝佐剂的情况下，TrV-VLPs 能够优先诱导 IgG2b 和 IgG3 型抗体。事实上，铝的使用并不干扰抗 TrV-VLPs 的总 IgG 谱。有趣的是，当与 TrV-VLPs 混合时，mix-IBMP 具有更好的总 IgG、IgG1 和 IgG3 亚类谱。
总之，这些结果表明 TrV-VLPs 作为疫苗佐剂的潜力以及使用 T. cruzi 嵌合抗原作为开发针对恰加斯病实验模型的疫苗的合理策略。
