Biology-Basel
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2025
·Vol. 14
·期 5
·563
·
IF 3.5
Lisha Ye,Simin Wu,Fuqiang Liu,Juan Zhang,Jie Wan,Chunqun Wang,Hui Liu,Min Hu
Simple SummaryHaemonchosis, caused byHaemonchus contortus, is a major parasitic disease in ruminants. The heavy reliance on anthelmintics has exacerbated drug resistance, making vaccine development imperative. H11 protein, a dominant antigen, confers partial immune protection to the host, but its formulation with the conventional QuilA adjuvant requires periodic booster immunizations. This study aimed to develop novel nano-adjuvants to enhance protective efficacy and prolong protection duration. Findings indicated that an immunostimulating complex matrix (IMX) combined with H11 protein elicited robust humoral immunity and durable immune memory in the host.The only vaccine againstHaemonchus contortusis limited by short-lived antibody persistence and the need for frequent booster immunizations. This study leveraged the advantages of nano-adjuvants in enhancing antigen presentation and immune regulation to evaluate the efficacy of novel adjuvants (IMX, AddaS03) and the conventional QuilA combined with H11 protein. Goats were divided into four groups (IMX + H11, AddaS03 + H11, QuilA + H11, and infected control). They were immunized three times and challenged with 6000 infective third-stage larvae (iL3s) ofH. contortuson the day of the third immunization, with the experiment lasting for 98 days. The results showed that vaccination with IMX + H11 conferred the strongest protection, demonstrating 88.3% efficacy in fecal egg count (FEC) reduction and 75.8% efficacy against worm burden, followed by QuilA + H11 (85.2% FEC reduction and 68% worm burden reduction) and AddaS03 + H11 (79.4% FEC reduction and 61.3% worm burden reduction). Serum IgG analysis revealed high antibody levels in all immunized groups. Cytokine detection found that IMX + H11 significantly upregulated IL-2 and IFN-γ expression in PBMCs and TNF-α expression in splenocytes, activating Th1-type responses and immune memory. QuilA + H11 showed weaker Th1 activation, and AddaS03 + H11 faced limitations due to insufficient antibody persistence for long-term protection. These findings suggest that IMX can induce highly efficient humoral and cellular immunity, providing a new direction for the optimization ofH. contortusvaccines and suggesting the importance of nano-adjuvants for precise regulation of immune patterns.
研究领域:
寄生虫学
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疫苗学
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免疫学
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PubMed
高影响因子
International Journal of Nanomedicine
·
2021
·
IF 6.4
Qiangqiang Wang,Xiaoke Sun,Xin Huang,Jianmei Huang,Muhammad Waqqas Hasan,RuoFeng Yan,Lixin Xu,Xiaokai Song,Xiangrui Li
Background Hepatocellular carcinoma-associated antigen 59 (HCA59) from excretory/secretory products of Haemonchus contortus is known to have the ability to modulate the functions of host cells. However, its immunogenicities using different nanoparticles adjuvants remain poorly understood. Purpose The study aimed to select an efficient nanoparticle antigen delivery system, which could enhance the immune responses of Haemonchus contortus HCA59 in mice. Methods Here, the immune responses induced by the recombinant protein of HCA59 (rHCA59) with poly-D,L-lactide-co-glycolide (PLGA) nanoparticles, Chitosan nanoparticles, mixture of PLGA and Chitosan nanoparticles (rHCA59-Chitosan-PLGA), and Freund’s complete adjuvant were observed, respectively, in mice. Cytokine and antibody levels induced by different groups were detected by ELISA assay. The effects of lymphocyte proliferations on different groups were examined using CCK-8 kit. Phenotypes of T cells and dendritic cells were analyzed by flow cytometry. Results On day 14 post vaccination, levels of IgM, IgG1, IgG2a, IFN-γ, IL-4, and IL-17 were significantly increased in the groups immunized with rHCA59 encapsulated with nanoparticles. After mice were vaccinated with rHCA59 loaded with Chitosan/PLGA nanoparticles, lymphocytes proliferated significantly. Additionally, the percentages of CD4 + T cells (CD3 + CD4 + ), CD8 + T cells (CD3 + CD8 + ), and dendritic cells (CD11c + CD83 + , CD11c + CD86 + ) were obviously up-regulated in the mice immunized with nanoparticles, especially in the rHCA59-Chitosan-PLGA antigen delivery system group. Conclusion The findings of this research demonstrated that rHCA59-Chitosan-PLGA antigen delivery system could induce higher immune responses in mice model and indicated that rHCA59 might be a good candidate molecule to develop nanovaccines against Haemonchus contortus in future study.
研究领域:
寄生虫学
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免疫学
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疫苗研究
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DOI
PubMed
高影响因子
PARASITOLOGY RESEARCH
·
2019
·Vol. 118
·期 4
·1239-1248
·
IF 2.067
Chen Jinglong,Ma Fuli,Li Xiangrui,Zhao Ruqian,Yang Xiaojing
Haemonchus contortus is a highly pathogenic gastrointestinal nematode of small ruminant animals. In modern intensive farming, livestock often suffer from different types of stress. However, whether host stress hormones influence H. contortus infection is largely unknown. Therefore, we treated H. contortus with norepinephrine (NE) and analyzed the changes in its excretory/secretory products (ESPs). Label-free quantitative proteomic analysis was used to identify differences in body proteins and ESPs between the control and NE-treated groups. We also investigated the changes in ESP action by analyzing cytokine secretion and goat peripheral blood mononuclear cell (PBMC) proliferation after incubation with ESPs secreted by NE-treated H. contortus . Thirty-two proteins in the body samples and 137 in the ESPs were differentially expressed between the groups. Gene ontology (GO) annotation showed that the functions of these different proteins might be involved in energy metabolism, protein metabolism, lipid metabolism, redox homeostasis, ion channel, and cell structure. NE treatment caused oxidative stress in H. contortus and changed the expression levels of some immunogenic proteins, such as the 15-kDa ESP . Meanwhile, the ESPs secreted by NE-treated H. contortus significantly decreased PBMC proliferation and the interleukin (IL)-2, IL-4, and interferon-gamma contents. Thus, NE treatment significantly affected the H. contortus body and ESP expression, and changes in the ESPs influenced PBMC function. The results reveal a relationship between host hormones and parasites and provide new clues to explain some of the variation in individual responses to infection.
研究领域:
寄生虫学
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兽医学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Lisha Ye,Tianjiao Wang,Simin Wu,Hui Liu,Feng Liu,Chunqun Wang,Min Hu
The intestinal native protein H11 is one of the most immunodominant antigen of Haemonchus contortus . However, H11 combined with QuilA adjuvant shows only short-lived protection for animals. Nano-adjuvants have the huge potential to extend the immune response in human and animals. Here, we compared the immune responses induced by H11 combined with three nano-adjuvants including lipid nanoparticles (LNP), immunostimulating complex matrix (IMX) and AddaS03™. We measured the cytokine levels of goat PBMCs stimulated by H11 mixed with three nano-adjuvants and QuilA. Results showed that the transcriptions of IL-6, IL-8 and IFN-γ genes were significantly inhibited in all adjuvant group compared with PBS control. H11-IMX combination significantly up-regulated IL-2, IL-17 and TNF-α gene transcriptions. The H11-LNP group showed a significant increase in IL-17 and TNF-α transcriptions, while the H11-AddaS03™ group significantly increased IL-2 transcription. Additionally, mice immunized with these formulations were assessed for splenic lymphocyte proliferation. All H11-adjuvant combinations, except H11-LNP, significantly stimulated lymphocyte proliferation compared to the H11 alone and PBS control groups, with the H11-AddaS03™ combination showing the strongest effect. Analysis of serum antibody levels revealed that all immune groups induced high IgM levels, with H11-IMX inducing the highest IgG levels. Our results demonstrated that IMX or LNP combined with H11 mainly induced a Th17 cell immune response in goat PBMCs, while IMX or AddaS03™ combined with H11 could induce a strong humoral immune response in mice. This study elucidates the immune response profiles of different nano-adjuvant combined with H11 antigen, providing important insights for vaccine development against parasitic nematodes.
研究领域:
寄生虫学
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免疫学
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疫苗开发
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DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2024
·
IF 2.6
Muhammad Waqqas Hasan,Muhammad Haseeb,Javaid Ali Gadahi,Muhammad Ehsan,Qiangqiang Wang,Shakeel Ahmed Lakho,Ali Haider,Muhammad Tahir Aleem,Kalibixiati Aimulajiang,Mingmin Lu,Lixin Xu,Xiaokai Song,Xiangrui Li,Ruofeng Yan
Haemonchus contortus poses a global challenge as a parasite affecting small ruminants, yet the problem of absence of an effective vaccine against H. contortus infection still exists. This investigation sought to appraise the immunological reaction induced by recombinant H. contortus excretory/secretory-24 (rHcES-24) in combination with complete Freund’s adjuvant (CFA) and bio-polymeric nanoparticles (NPs) within a murine model. In this study, rHcES-24 was encapsulated in poly(d, l-lactide-co-glycolide) (PLGA) and chitosan (CS) NPs, administered subcutaneously to mice. Researchers analyzed the NPs using scanning electron microscope (SEM) and assessed lymphocyte proliferation, specific antibodies, cytokines, T cell proliferation (CD3e+CD4+, CD3e+CD8a+), and phenotypic alteration in splenocytes (CD11c+CD83+, CD11c+CD86+) through flow cytometry to understand the immune response. The results demonstrated that the administration of nanovaccines (NVs) prompted immune responses towards Th1 pathway. This was indicated by notable enhancements in the production of specific antibodies, heightened cytokine levels, and a robust proliferation of lymphocytes observed in mice that received the NVs compared to control groups. Remarkably, mice vaccinated with the antigen-loaded NPs formulations exhibited considerably higher proportions of splenic dendritic cells (DCs) and T cells in comparison to those receiving the traditional adjuvant or the control groups. Incorporating HcES-24 protein into NPs effectively conferred immunity against H. contortus, paving the way for developing a targeted and commercial vaccine.
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PubMed
高影响因子
Vaccines
·
2020
·Vol. 8
·期 4
·726
·
IF 4.086
Muhammad Waqqas Hasan,Muhammad Haseeb,Muhammad Ehsan,Javaid Ali Gadahi,Muhammad Ali-ul-Husnain Naqvi,Qiang Qiang Wang,Xinchao Liu,Shakeel Ahmed Lakho,Ruofeng Yan,Lixin Xu,Xiaokai Song,Xiangrui Li
ADP-ribosylation factor 1 (HcARF1) is one of theHaemonchus contortus(H. contortus) excretory/secretory proteins involved in modulating the immune response of goat peripheral blood mononuclear cells (PBMC). Here, we evaluated the immunogenic potential of recombinant HcARF1 (rHcARF1) againstH. contortusinfection in Institute of Cancer Research (ICR) mice. Briefly, rHcARF1 was entrapped in poly (D, L-lactide-co-glycolide) (PLGA) and chitosan (CS) nanoparticles (NP) and injected into mice as a vaccine. Fifty-six ICR mice were assigned randomly into seven groups, with eight animals in each group, and they were vaccinated subcutaneously. At the end of the experiment (14th day), the blood and the spleen were collected from euthanized mice to detect lymphocyte proliferation, cytokine analysis, and the production of antigen-specific antibodies. Scanning electron microscope was used to determine the size, morphology, and zeta potential of nanoparticles. Flow cytometry was performed, which presented the increase percentages of CD4+T cells (CD3e+CD4+), CD8+T cells (CD3e+CD8+) and dendritic cells (CD11c+CD83+, CD11c+CD86+) in mice vaccinated with rHcARF1+PLGA NP. Immunoassay analysis show raised humoral (Immunoglobulin (Ig)G1, IgG2a, IgM) and cell-mediated immune response (Interleukin (IL)-4, IL-12, and IL-17, and Interferon (IFN)-γ) induced by rHcARF1+PLGA NP. Experimental groups that were treated with the antigen-loaded NP yield higher lymphocyte proliferation than the control groups. Based on these results, we could propose that the rHcARF1 encapsulated in NP could stimulate a strong immune response in mice rather than administering alone against the infection ofH. contortus.Keywords:Haemonchus contortus;rHcARF1;PLGA;CS;nanoparticle;ICR mice
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高影响因子
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