Gharaei Abdolaziz, Rahdar Mahmoud, Jorjani Oghlniaz, Saberi Sedigheh, Beiromvand Molouk, Feiz-Haddad Mohammad Hossein
Infecti ous and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 15794-61357, Iran.
Department of Medical Parasitology, Medical school, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran.
Trans R Soc Trop Med Hyg. 2025 Mar 7;119(3):266-273. doi: 10.1093/trstmh/trae126.
Leishmaniasis represents a significant parasitic disease with global health implications, and the development of an affordable and effective vaccine could provide a valuable solution. This study aimed to evaluate the immunogenicity of a DNA vaccine targeting Leishmania major specifically based on the Leishmania-activated C kinase (LACK) antigen, utilizing calcium phosphate nanoparticles (CaPNs) and chitosan nanoparticles (ChitNs) as adjuvants.
Seventy female BALB/c mice, aged 4-6 wk and weighing 20-22 g, were selected and divided into five groups, each consisting of 14 mice. The first group received the plasmid LACK vaccine (pcDN3+LACK), the second group received the pcDN3+LACK vaccine with the CaPN adjuvant (pcDN3+LACK+CaPN), the third group received the pcDN3+LACK vaccine with the ChitN adjuvant (pcDN3+LACK+ChitN), the fourth group was administered phosphate-buffered saline as a negative control and the fifth group did not receive any vaccine, serving as a positive control. The vaccination program involved two intramuscular injections at 3-wk intervals. Three weeks following the final vaccination, the mice were challenged with wild-type L. major promastigotes via intradermal injection at the base of their tails. Clinical signs and lesion sizes were evaluated biweekly using Vernier calipers. Immune responses, including levels of interferon-gamma (IFN-γ) and interleukin-4 (IL-4), were assessed using ELISA.
The groups receiving pcDN3+LACK+ChitN, pcDN3+LACK+CaPN and pcDN3+LACK exhibited the highest increases in IFN-γ titers and the most significant reductions in IL-4 titers. Furthermore, lesion sizes associated with Leishmania infection were reduced in the vaccinated groups, with the most favorable outcomes observed in the pcDN3+LACK+ChitN group.
These findings suggest that vaccination utilizing the LACK antigen in conjunction with CaPN and ChitN adjuvants may represent an effective strategy for the control of cutaneous leishmaniasis.
利什曼病是一种对全球健康有重大影响的寄生虫病，开发一种经济有效的疫苗可能是一个有价值的解决方案。本研究旨在评估一种基于利什曼原虫激活的C激酶（LACK）抗原的针对硕大利什曼原虫的DNA疫苗的免疫原性，使用磷酸钙纳米颗粒（CaPNs）和壳聚糖纳米颗粒（ChitNs）作为佐剂。
选取70只4-6周龄、体重20-22 g的雌性BALB/c小鼠，分为五组，每组14只。第一组接受质粒LACK疫苗（pcDN3+LACK），第二组接受含CaPN佐剂的pcDN3+LACK疫苗（pcDN3+LACK+CaPN），第三组接受含ChitN佐剂的pcDN3+LACK疫苗（pcDN3+LACK+ChitN），第四组给予磷酸盐缓冲盐水作为阴性对照，第五组不接受任何疫苗，作为阳性对照。疫苗接种方案包括每隔3周进行两次肌肉注射。最后一次接种后3周，通过在小鼠尾巴根部皮内注射野生型硕大利什曼原虫前鞭毛体对小鼠进行攻击。每两周使用游标卡尺评估临床症状和病变大小。使用酶联免疫吸附测定法评估免疫反应，包括γ干扰素（IFN-γ）和白细胞介素-4（IL-4）水平。
接受pcDN3+LACK+ChitN、pcDN3+LACK+CaPN和pcDN3+LACK的组IFN-γ滴度升高最高，IL-4滴度降低最显著。此外，接种组中与利什曼原虫感染相关的病变大小减小，在pcDN3+LACK+ChitN组中观察到最有利的结果。
这些发现表明，使用LACK抗原结合CaPN和ChitN佐剂进行疫苗接种可能是控制皮肤利什曼病的有效策略。
