Evaluation of the immunogenicity of a DNA vaccine for Leishmania major based on the Leishmania-activated C kinase antigen using calcium phosphate and chitosan adjuvants.

IF 1.9 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
Abdolaziz Gharaei, Mahmoud Rahdar, Oghlniaz Jorjani, Sedigheh Saberi, Molouk Beiromvand, Mohammad Hossein Feiz-Haddad
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

基于利什曼活化C激酶抗原、磷酸钙和壳聚糖佐剂的大利什曼原虫DNA疫苗免疫原性评价
背景:利什曼病是一种影响全球健康的重要寄生虫病,开发一种负担得起的有效疫苗可能提供一种有价值的解决办法。本研究利用磷酸钙纳米粒(CaPNs)和壳聚糖纳米粒(ChitNs)作为佐剂,以利什曼原虫活化的C激酶(LACK)抗原为基础,对一种靶向利什曼原虫的DNA疫苗的免疫原性进行了评价。方法:选取年龄4 ~ 6周龄、体重20 ~ 22 g的BALB/c雌性小鼠70只,分为5组,每组14只。第1组接种质粒LACK疫苗(pcDN3+LACK),第2组接种pcDN3+LACK+CaPN佐剂疫苗(pcDN3+LACK+CaPN),第3组接种pcDN3+LACK+ChitN佐剂疫苗(pcDN3+LACK+ChitN),第4组接种磷酸盐缓冲盐水作为阴性对照,第5组不接种任何疫苗作为阳性对照。疫苗接种计划包括每隔3周进行两次肌肉注射。在最后一次接种三周后,小鼠通过尾根部皮内注射野生型大原乳杆菌。每两周使用游标卡尺评估临床症状和病变大小。免疫应答,包括干扰素-γ (IFN-γ)和白细胞介素-4 (IL-4)水平,采用ELISA评估。结果:pcDN3+LACK+ChitN、pcDN3+LACK+CaPN和pcDN3+LACK组IFN-γ滴度升高最高,IL-4滴度降低最显著。此外,接种疫苗组与利什曼原虫感染相关的病变大小减小,在pcDN3+LACK+ChitN组观察到最有利的结果。结论:这些发现表明,利用LACK抗原与CaPN和ChitN佐剂联合接种疫苗可能是控制皮肤利什曼病的有效策略。
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来源期刊
Transactions of The Royal Society of Tropical Medicine and Hygiene
Transactions of The Royal Society of Tropical Medicine and Hygiene 医学-公共卫生、环境卫生与职业卫生
CiteScore
4.00
自引率
9.10%
发文量
115
审稿时长
4-8 weeks
期刊介绍: Transactions of the Royal Society of Tropical Medicine and Hygiene publishes authoritative and impactful original, peer-reviewed articles and reviews on all aspects of tropical medicine.
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