Araújo Marcelo Valdemir de, Santos Júnior Samuel Rodrigues Dos, Nosanchuk Joshua D, Taborda Carlos Pelleschi
Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, Brazil.
Departments of Medicine (Division of Infectious Disease), Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA.
J Fungi (Basel). 2020 Dec 8;6(4):347. doi: 10.3390/jof6040347.
The peptide P10 is a vaccine candidate for Paracoccidioidomycosis, a systemic mycosis caused by fungal species of the genus spp. We have previously shown that peptide P10 vaccination, in the presence of several different adjuvants, induced a protective cellular immune response mediated by CD4 Th lymphocytes that was associated with the increased production of IFN-γ in mice challenged with a virulent isolate of . Cationic liposomes formulated with dioctadecyldimethylammonium and trehalose dibehenate (DDA/TDB, termed also CAF01-cationic adjuvant formulation) have been developed for safe administration in humans and CAF01 liposomes are utilized as an adjuvant for modulating a robust Th/Th cellular response. We evaluated the efficacy of the adsorption of peptide P10 to CAF01 cationic liposomes and used the generated liposomes to vaccinate C57Bl/6 mice infected with . Our results showed that P10 was efficiently adsorbed onto CAF01 liposomes. The vaccination of infected mice with cationic liposomes formulated with DDA/TDB 250/50 µg/mL and 20 µg of P10 induced an effective cellular immune response with increased levels of Th cytokines, which correlated with significant decreases in the fungal burdens in lungs and protective granulomatous tissue responses. Hence, cationic liposomes of DDA/TDB 250/50 µg/mL with 20 µg of P10 are a promising therapeutic for safely and effectively improving the treatment of paracoccidioidomycosis.
肽P10是用于治疗副球孢子菌病的候选疫苗，副球孢子菌病是一种由副球孢子菌属真菌引起的系统性真菌病。我们之前已经表明，在几种不同佐剂存在的情况下，肽P10疫苗接种可诱导由CD4 Th淋巴细胞介导的保护性细胞免疫反应，这与用强毒株攻击的小鼠中IFN-γ产量增加有关。已开发出用二辛基二甲基氯化铵和山嵛酸海藻糖（DDA/TDB，也称为CAF01阳离子佐剂配方）配制的阳离子脂质体，以便在人体中安全给药，并且CAF01脂质体用作调节强大的Th1/Th17细胞反应的佐剂。我们评估了肽P10吸附到CAF01阳离子脂质体上的效果，并使用生成的脂质体对感染了副球孢子菌的C57Bl/6小鼠进行疫苗接种。我们的结果表明，P10能有效地吸附到CAF01脂质体上。用含有250/50 µg/mL DDA/TDB和20 µg P10配制的阳离子脂质体对感染小鼠进行疫苗接种，可诱导有效的细胞免疫反应，Th细胞因子水平升高，这与肺部真菌负荷显著降低以及保护性肉芽肿组织反应相关。因此，含有20 µg P10的250/50 µg/mL DDA/TDB阳离子脂质体是安全有效地改善副球孢子菌病治疗的一种有前景的疗法。
