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Local and Systemic Antibody Responses in Mice Immunized Intranasally with Native and Detergent-Extracted Outer Membrane Vesicles from Neisseria meningitidis

机译：经脑膜炎奈瑟氏球菌天然和洗涤剂提取的外膜囊泡经鼻腔免疫的小鼠的局部和全身抗体反应

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The mouse humoral immune response toward native or detergent-extracted outer membrane vesicles (NOMVs and DOMVs, respectively) from Neisseria meningitidis was determined after intranasal immunization. Both preparations elicited high frequencies of NOMV-specific antibody-forming cells (AFCs) locally in the nasal associated lymphoid tissue (NALT) after three or four weekly doses. The diffuse NALT (D-NALT) contained ca. 10-fold more NOMV-specific AFCs than those observed in the mediastinal lymph node, spleen, and bone marrow. AFCs observed in the D-NALT were primarily immunoglobulin A positive (IgA+) and were maintained for at least 1 month. In contrast, the organized NALT (O-NALT) contained low numbers of AFCs, and the response was relatively short-lived. In other lymphoid tissues, AFCs producing various IgG subclasses and IgM were present with IgG2b-producing AFCs being dominant or codominant with IgA or IgG2a. In serum and in all of the tissues examined, with the exception of the NALT, NOMVs clearly induced a stronger antibody response and a broader range of antibody isotypes than DOMVs. The development of NOMV-specific AFCs in spleen and bone marrow after intranasal immunization was slow compared to intravenous immunization but, once established, the intranasally elicited responses increased steadily for at least 75 days. NOMV-specific antibodies induced via several routes of immunization had high bactericidal activities in serum. Our results indicated that intranasally administered OMVs induced strong local and systemic antibody responses in mice that were relatively long-lived.
机译：鼻内免疫后，确定对脑膜炎奈瑟氏球菌天然或去污剂提取的外膜囊泡（分别为NOMV和DOMV）的小鼠体液免疫应答。两种制剂在每周三或四周的剂量后在与鼻相关的淋巴组织（NALT）中局部引起高频率的NOMV特异性抗体形成细胞（AFC）。弥散性NALT（D-NALT）包含约。 NOMV特异AFC比在纵隔淋巴结，脾脏和骨髓中观察到的多10倍。在D-NALT中观察到的AFC主要是免疫球蛋白A阳性（IgA +），并维持至少1个月。相反，有组织的NALT（O-NALT）包含的AFC数量少，且响应时间相对较短。在其他淋巴组织中，存在产生各种IgG亚类和IgM的AFC，而产生IgG2b的AFC与IgA或IgG2a占优势或共存。在血清和所有检查的组织中，除NALT外，NOMV明显比DOMV诱导更强的抗体反应和更广泛的抗体同种型。与静脉内免疫相比，鼻内免疫后脾脏和骨髓中NOMV特异性AFC的发展缓慢，但是一旦建立，鼻内引起的反应至少会稳定增加75天。通过几种免疫途径诱导的NOMV特异性抗体在血清中具有很高的杀菌活性。我们的结果表明，鼻内给药的OMV在寿命相对较长的小鼠中引起强烈的局部和全身抗体反应。

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