Mucosal Vaccination with Lactococcus lactis-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B Streptococcus in a Murine Model

Mucosal Vaccination with Lactococcus lactis-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B Streptococcus in a Murine Model
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DOI:
10.3390/vaccines8020146
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发表时间:
2020-06-01
期刊:
影响因子:
7.8
通讯作者:
Vasquez, Abel E.
Vasquez, Abel E.
中科院分区:
医学3区
文献类型:
--
作者:
Diaz-Dinamarca, Diego A.;Hernandez, Carlos;Vasquez, Abel E.

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b族链球菌(GBS)是新生儿败血症和脑膜炎的主要病原,与早产和死产有关。开发一种获得许可的疫苗是世界卫生组织面临的未决挑战之一。在此之前,我们发现口服免疫表面免疫蛋白(SIP)可以减少GBS的阴道定植,并产生功能性调理抗体,这是通过体外调理噬细胞测定(OPA)来确定的。我们还发现该蛋白具有佐剂疫苗的特征。因此,基于SIP的口服疫苗可能是开发针对GBS的新疫苗的一个有吸引力的替代方案。乳酸乳球菌是一种突出的口服疫苗益生菌诱导粘膜免疫反应。这种细菌可以作为一种抗原传递载体,用于开发一种可食用疫苗,并已用于临床试验。在这项研究中,我们展示了一种含重组l的口服疫苗。从GBS (rL)分泌SIP的乳酸菌株。在C57BL/6小鼠阴道定殖实验模型中,乳酸- sip可诱导保护性体液免疫和细胞免疫。用l免疫的小鼠。乳酸菌- sip对GBS阴道定植后的临床症状和细菌定植有保护作用。OurrL。乳酸-SIP疫苗还可诱导免疫球蛋白G (IgG)和免疫球蛋白A (IgA)特异性升高。将疫苗小鼠的血清过继转移到幼稚小鼠体内,可产生抵抗GBS阴道定植的保护作用。此外,therL。lactis-SIP菌株可诱导sip特异性T细胞活化,减少GBS阴道定植,并在转移到其他小鼠体内时产生保护性抗体。我们的实验观察有力地支持了rl。乳酸- sip可诱导保护性体液和细胞免疫,可被认为是开发GBS疫苗的一种新选择。
Group BStreptococcus(GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed that oral immunization with surface immune protein (SIP) decreases vaginal colonization of GBS and generates functional opsonizing antibodies, which was determined by opsonophagocytic assays (OPA) in vitro. We also showed that the protein has an adjuvant vaccine profile. Therefore, an oral vaccine based on SIP may be an attractive alternative to employ in the development of new vaccines against GBS.Lactococcus lactisis a highlighted oral vaccine probiotic inducer of the mucosal immune response. This bacterium could serve as an antigen-delivering vehicle for the development of an edible vaccine and has been used in clinical trials. In this study, we showed that an oral vaccine with a recombinantL. lactisstrain secreting SIP from GBS (rL. lactis-SIP) can induce protective humoral and cellular immunity in an experimental model of GBS vaginal colonization in C57BL/6 mice. Mice immunized withrL. lactis-SIP were protected against clinical symptoms and bacterial colonization after GBS vaginal colonization. OurrL. lactis-SIP vaccine also induces an increase of immunoglobulin G (IgG) and immunoglobulin A (IgA) specifically against SIP. The adoptive transfer of serum from vaccinated mice to naive mice generated protection against GBS vaginal colonization. Moreover, therL.lactis-SIP strain induces the activation of SIP-specific T cells, which could decrease GBS vaginal colonization and generate protective antibodies when transferred to other mice. Our experimental observations strongly support the notion thatrL. lactis-SIP induces protective humoral and cellular immunity and could be considered as a novel alternative in the development of vaccines for GBS.