{"title":"Effects of different immunomodulating liposome-based adjuvants and injection sites on immunogenicity in pigs","authors":"Evelína Šťastná , Gitte Erbs , Kerstin Skovgaard , Jeanne Toft Jakobsen , Mick Bailey , Gabriel Kristian Pedersen , Gregers Jungersen","doi":"10.1016/j.micinf.2024.105346","DOIUrl":null,"url":null,"abstract":"<div><p>Vaccine adjuvants, such as liposome-based cationic adjuvant formulations (CAFs), are able to boost immune responses and, by incorporation of distinct immunomodulators, steer immunity towards a desired direction in mice, non-human primates and humans, while less studied in pigs. Here we used commercial pigs to investigate polarizing adjuvant effects of CAFs with immunomodulators: C-type lectin receptor ligands trehalose-6,6ʼ-dibehenate and monomycolyl glycerol, toll-like receptor 3 ligand Poly(I:C) or retinoic acid. Vaccines were formulated with a recombinant <em>Chlamydia</em> model protein antigen and administered via three injection routes. All adjuvants significantly increased antigen-specific IgG in serum, compared to non-adjuvanted antigen. Administering the vaccines through intramuscular and intraperitoneal routes induced significantly higher antigen-specific IgG and IgA serum antibodies, than the perirectal route. Although immunizations triggered cell-mediated immunity, no significant differences between adjuvants or injection sites were detected. Genes depicting T cell subtypes revealed only minor differences. Our findings suggest that specific signatures of the tested adjuvant immunomodulation do not translate well from mice to pigs in standard two-dose immunizations. This study provides new insights into immune responses to CAFs in pigs, and highlights that adjuvant development should ideally be carried out in the intended species of interest or in models with high predictive validity/translational value.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924000765/pdfft?md5=d28093bc6978156731bd85958e64fa71&pid=1-s2.0-S1286457924000765-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbes and Infection","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1286457924000765","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Vaccine adjuvants, such as liposome-based cationic adjuvant formulations (CAFs), are able to boost immune responses and, by incorporation of distinct immunomodulators, steer immunity towards a desired direction in mice, non-human primates and humans, while less studied in pigs. Here we used commercial pigs to investigate polarizing adjuvant effects of CAFs with immunomodulators: C-type lectin receptor ligands trehalose-6,6ʼ-dibehenate and monomycolyl glycerol, toll-like receptor 3 ligand Poly(I:C) or retinoic acid. Vaccines were formulated with a recombinant Chlamydia model protein antigen and administered via three injection routes. All adjuvants significantly increased antigen-specific IgG in serum, compared to non-adjuvanted antigen. Administering the vaccines through intramuscular and intraperitoneal routes induced significantly higher antigen-specific IgG and IgA serum antibodies, than the perirectal route. Although immunizations triggered cell-mediated immunity, no significant differences between adjuvants or injection sites were detected. Genes depicting T cell subtypes revealed only minor differences. Our findings suggest that specific signatures of the tested adjuvant immunomodulation do not translate well from mice to pigs in standard two-dose immunizations. This study provides new insights into immune responses to CAFs in pigs, and highlights that adjuvant development should ideally be carried out in the intended species of interest or in models with high predictive validity/translational value.
疫苗佐剂,如基于脂质体的阳离子佐剂制剂(CAFs),能够增强免疫反应,并通过加入不同的免疫调节剂,将小鼠、非人灵长类动物和人类的免疫引导至所需的方向,但对猪的研究较少。在这里,我们用商品猪来研究含有免疫调节剂的 CAFs 的极化佐剂效应:C型凝集素受体配体三卤糖-6,6ʼ-二苯甲酸酯和甘油单甲酯、收费样受体3配体Poly(I:C)或维甲酸。疫苗采用重组衣原体模型蛋白抗原配制,通过三种注射途径给药。与未添加佐剂的抗原相比,所有佐剂都能明显增加血清中的抗原特异性 IgG。通过肌肉注射和腹膜内注射途径接种疫苗,诱导的抗原特异性 IgG 和 IgA 血清抗体明显高于直肠周围途径。虽然免疫接种会引发细胞介导免疫,但不同佐剂或注射部位之间并无明显差异。描述 T 细胞亚型的基因仅显示出微小差异。我们的研究结果表明,在标准的两剂免疫接种中,测试佐剂免疫调节的特定特征并不能很好地从小鼠转化到猪。这项研究为猪对CAFs的免疫反应提供了新的见解,并强调了佐剂的开发最好在目标物种或具有高预测效力/翻译价值的模型中进行。
期刊介绍:
Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular:
the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms.
the immune response to infection, including pathogenesis and host susceptibility.
emerging human infectious diseases.
systems immunology.
molecular epidemiology/genetics of host pathogen interactions.
microbiota and host "interactions".
vaccine development, including novel strategies and adjuvants.
Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal.
Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.