Liposome-based dry powder vaccine immunization targeting the lungs induces broad protection against pneumococcus
Liposome-based dry powder vaccine immunization targeting the lungs induces broad protection against pneumococcus
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DOI：
10.1016/j.jconrel.2024.02.028
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发表时间：
2024-02-24
影响因子：
10.8
通讯作者：
Miyaji，E. N.
中科院分区：
文献类型：
--
作者：
Rodrigues，T. C.;Figueiredo，D. B.;Miyaji，E. N.
肺炎链球菌是一种重要的人类病原体。目前使用的结合疫苗对侵袭性疾病有效，但保护仅限于配方中包含的血清型，导致血清型替代。此外，据报道，对非侵入性疾病的保护要低得多。因此，开发一种血清型无关的疫苗是很重要的，肺炎球菌表面蛋白a （PspA）是一种很有前途的候选疫苗。PspA具有一定的多样性，可分为3科6支，其中科1和科2在临床分离株中最常见。因此，理想的疫苗应该对两种最常见的PspA家族产生保护作用。这项工作的目的是开发一种含有pspa家族1和2的基于脂质体的疫苗，并表征其免疫反应。采用微流体技术制备了含有α-半乳糖神经酰胺（α-GalCer）或不含α-半乳糖神经酰胺（α-GalCer）的双棕榈酰磷脂酰胆碱（DPPC）和3β-[N-（N ',N ' -二甲氨基乙烷）-氨基甲酰基]胆固醇（DC-Chol）脂质体（LP），将进化枝1 （PspA1，家族1）和/或进化枝4 （PspA4Pro，家族2）的PspA包封，然后用海藻糖喷雾干燥形成纳米复合微粒载体（NCMP）。LP/NCMPs具有良好的稳定性和保存活性。含有PspA1和/或PspA4Pro的LP/NCMPs用于靶向肺的小鼠免疫。用含有α-GalCer的LP/NCMPs免疫的动物血清中均检测到高的抗PspA1和PspA4Pro的IgG抗体滴度，且IgG1和IgG2a滴度平衡。免疫小鼠血清中IgG与不同血清型和表达不同PspA支系的肺炎球菌菌株结合，表明具有广泛的识别性。同时检测粘膜IgG和IgA。重要的是，LP/NCMPs免疫诱导了对表达家族1和家族2 pspa的菌株的充分保护。此外，在免疫动物的肺部检测到CD4+常驻记忆T细胞。
Streptococcus pneumoniaeis an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4+resident memory T cells were detected in the lungs of the immunized animals that survived the challenge.