Ottino Jennifer, Leite Jaqueline Costa, Melo-Júnior Otoni Alves, González Marco Antonio Cabrera, Carvalho Tatiane Furtado de, Garcia Giani Martins, Batista Maurício Azevedo, Silveira Patrícia, Cardoso Mariana Santos, Bueno Lilian Lacerda, Fujiwara Ricardo Toshio, Santos Renato Lima, Paes Paulo Ricardo de Oliveira, Silveira-Lemos Denise, Martins-Filho Olindo Assis, Galdino Alexsandro Sobreira, Chávez-Fumagalli Miguel Angel, Dutra Walderez Ornelas, Mosqueira Vanessa Carla Furtado, Giunchetti Rodolfo Cordeiro
Departamento de Parasitologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, Brazil.
Departamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, Brazil.
Vaccines (Basel). 2022 Oct 31;10(11):1848. doi: 10.3390/vaccines10111848.
Leishmaniasis is a widespread vector-borne disease in Brazil, with () as the primary etiological agent of visceral leishmaniasis (VL). Dogs are considered the main reservoir of this parasite, whose treatment in Brazil is restricted to the use of veterinary medicines, which do not promote a parasitological cure. Therefore, efficient vaccine development is the best approach to Canine Visceral Leishmaniasis (CVL) control. With this in mind, this study used hamsters () as an experimental model in an anti- preclinical vaccine trial to evaluate the safety, antigenicity, humoral response, and effects on tissue parasite load. Two novel formulations of nanoparticles made from poly(D, L-lactic) acid (PLA) polymer loading crude antigen (LB) exhibiting two different particle sizes were utilized: LBPSmG (570 nm) and LBPSmP (388 nm). The results showed that the nanoparticles were safe and harmless to hamsters and were antigenic with the induction in LBSap, LBPSmG, and LBPSmG groups of total anti- IgG antibodies 30 days after challenge, which persists 200 days in LBSap and LBPSmP. At the same time, a less pronounced hepatosplenomegaly in LBSap, LBPSmG, and LBPSmP was found when compared to control groups, as well as a less pronounced inflammatory infiltrate and granuloma formation in the spleen. Furthermore, significant reductions of 84%, 81%, and 90% were observed in spleen parasite burden accessed by PCR in the LBSap, LBPSmG, and LBPSmP groups, respectively. In this way, LBSap, LBPSmG, and LBPSmP formulations showed better results in vaccinated and -challenged animals in further reducing parasitic load in the spleen and attenuating lesions in liver and splenic tissues. This results in safe, harmless nanoformulation vaccines with significant immunogenic and infection control potential. In addition, animals vaccinated with LBPSmP had an overall reduction in parasite burden in the spleen, indicating that a smaller nanoparticle could be more efficient in targeting antigen-presenting cells.
利什曼病是巴西一种广泛传播的媒介传播疾病，（）是内脏利什曼病（VL）的主要病原体。狗被认为是这种寄生虫的主要宿主，在巴西，对狗的治疗仅限于使用兽用药物，这些药物无法实现寄生虫学治愈。因此，开发有效的疫苗是控制犬内脏利什曼病（CVL）的最佳方法。考虑到这一点，本研究使用仓鼠（）作为实验模型，进行临床前抗疫苗试验，以评估安全性、抗原性、体液反应以及对组织寄生虫负荷的影响。使用了由聚（D，L-乳酸）（PLA）聚合物负载粗抗原（LB）制成的两种新型纳米颗粒制剂，它们呈现出两种不同的粒径：LBPSmG（570纳米）和LBPSmP（388纳米）。结果表明，纳米颗粒对仓鼠安全无害，具有抗原性，在攻击后30天，LBSap、LBPSmG和LBPSmG组诱导产生了总抗IgG抗体，在LBSap和LBPSmP组中该抗体持续存在200天。同时，与对照组相比，LBSap、LBPSmG和LBPSmP组的肝脾肿大不太明显，脾脏中的炎性浸润和肉芽肿形成也不太明显。此外，通过PCR检测发现，LBSap、LBPSmG和LBPSmP组脾脏中的寄生虫负荷分别显著降低了84%、81%和90%。这样，LBSap、LBPSmG和LBPSmP制剂在接种疫苗并受到攻击的动物中，在进一步降低脾脏中的寄生虫负荷以及减轻肝脏和脾脏组织的病变方面显示出更好的效果。这产生了具有显著免疫原性和感染控制潜力的安全无害纳米制剂疫苗。此外，用LBPSmP接种疫苗的动物脾脏中的寄生虫负荷总体降低，表明较小的纳米颗粒在靶向抗原呈递细胞方面可能更有效。
