中文摘要：本研究利用先前研究构建的NP/NCMP PspA4Pro免疫小鼠。NP/NCMP PspA4Pro由L-亮氨酸的微载体（纳米复合微粒-NCMPs）和源于PspA4Pr 分枝4的链球菌表面蛋白A的PGA-co-PDL多聚纳米颗粒构成。接种这种复合物后，能够诱导血浆和肺部产生抗PspA4Pro的IgG抗体。结果表明，采用NP/NCMP PspA4Pro进行粘膜免疫和皮下接种抗原蛋白均能诱导产生抗鼻内肺炎球菌特异性保护作用。尽管粘膜免疫和皮下注射抗原蛋白的存活率相似，但NP/NCMP PspA4Pro能够较早地控制感染。然而，无论哪种免疫方式在感染肺链球菌后都不能降低肺部细菌数量。采用NP/NCMP PspA4Pro进行粘膜免疫能够诱导产生组织性和系统性抗体，且只能产生抗表达PspA肺链球菌的保护作用。
 
外文摘要：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-omega-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.
外文关键词：STREPTOCOCCUS-PNEUMONIAE; INHALATIVE VACCINATION; COMPLEMENT DEPOSITION; PULMONARY INFECTION; CONJUGATE VACCINE; MICE; POLYSACCHARIDE; TUBERCULOSIS; RESPONSES; DELIVERY
作者：Rodrigues, TC; Oliveira, MLS; Soares-Schanoski, A; Chavez-Rico, SL; Figueiredo, DB; Goncalves, VM; Ferreira, DM; Kunda, NK; Saleem, IY; Miyaji, EN
作者单位：巴西布坦坦研究所
期刊名称：PLOS ONE
期刊影响因子：2.81
出版年份：2018
出版刊次：1
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