Rodrigues Tasson C, Oliveira Maria Leonor S, Soares-Schanoski Alessandra, Chavez-Rico Stefanni L, Figueiredo Douglas B, Gonçalves Viviane M, Ferreira Daniela M, Kunda Nitesh K, Saleem Imran Y, Miyaji Eliane N
Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil.
Laboratório Especial de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, SP, Brazil.
PLoS One. 2018 Jan 23;13(1):e0191692. doi: 10.1371/journal.pone.0191692. eCollection 2018.
Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2.
尽管有结合疫苗，但肺炎链球菌引起的肺炎负担仍然很高。针对肺部的粘膜免疫是诱导局部免疫反应以提高对肺炎保护作用的一种有吸引力的替代方法。我们小组之前描述了聚（己二酸甘油酯-共-ω-十五内酯）（PGA-co-PDL）聚合物纳米颗粒（NPs）的开发，该纳米颗粒吸附了来自4分支的肺炎球菌表面蛋白A（PspA4Pro），并包裹在L-亮氨酸微载体中（纳米复合微粒-NCMPs），用于靶向肺部的粘膜递送（NP/NCMP PspA4Pro）。现在使用NP/NCMP PspA4Pro对小鼠进行免疫。接种这种制剂可在血清和肺中诱导抗PspA4Pro IgG抗体。血清IgG与完整细菌结合的分析表明，它能有效结合表达来自3、4和5分支（第2家族）的PspA的细菌，但未观察到与表达来自1和2分支（第1家族）的PspA的细菌结合。用NP/NCMP PspA4Pro进行粘膜免疫和皮下注射该蛋白均可对用表达来自5分支的PspA（PspA5）的3型菌株进行鼻内致死性肺炎球菌攻击产生部分保护作用。尽管用NP/NCMP PspA4Pro进行粘膜免疫和用纯化蛋白进行皮下免疫观察到相似的存活水平，但NP/NCMP PspA4Pro诱导了对感染的更早控制。相反，在用表达来自1分支的PspA（PspA1）的19F型菌株攻击后，用NP/NCMP PspA4Pro免疫和用纯化蛋白皮下免疫均未降低肺中的细菌载量。因此，靶向肺部的用NP/NCMP PspA4Pro进行粘膜免疫能够诱导局部和全身抗体，仅对表达来自同源第2家族的PspA的菌株提供保护。
