PilVax, a novel Lactococcus lactis-based mucosal vaccine platform, stimulates systemic and mucosal immune responses to Staphylococcus aureus.,Immunology and Cell Biology

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PilVax, a novel Lactococcus lactis-based mucosal vaccine platform, stimulates systemic and mucosal immune responses to Staphylococcus aureus.
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2020-04-09 , DOI: 10.1111/imcb.12325
Fiona Clow ₁ , Kelly Peterken ₁ , Victoria Pearson ₁ , Thomas Proft ₁ , Fiona J Radcliff ₁

Affiliation

Most pathogens initiate infection via the mucosa, therefore delivery of vaccines directly to the mucosa is likely to be advantageous for stimulating protective immunity at the site of entry. PilVax is a novel mucosal vaccine platform that harnesses Lactococcus lactis bacteria engineered to stably express multiple copies of vaccine peptide antigens within pili, hair-like structures which extend from the cell wall. This strategy elicited systemic and mucosal antibody responses to a model antigen after intranasal immunization, but has not been tested for its capacity to stimulate protective mucosal immunity. A well-characterized linear B-cell epitope, D3(22-33) , from the fibronectin-binding protein A of Staphylococcus aureus was successfully introduced into PilVax and delivered intranasally to mice. Specific antipeptide immunoglobulin (Ig) G and IgA antibodies were detected in the serum and respiratory mucosa of vaccinated mice. Responses to the major pilus backbone protein Spy0128 were also assessed; robust antibody responses to this antigen were generated both systemically and in the respiratory and intestinal mucosa. Mice were challenged intranasally with the mouse-adapted S. aureus JSNZ strain and the S. aureus load quantified 7 days after challenge. Unexpectedly, exposure to PilVax, irrespective of the presence of the peptide, resulted in a significant reduction in S. aureus load in both the intestine and nasal mucosa (both P < 0.05) when compared with unvaccinated control mice. The mechanism(s) of protection are unclear, but merit further investigation to determine whether PilVax is a suitable platform for delivery of vaccine candidate antigens to the mucosa.

中文翻译：

PilVax 是一种基于乳酸乳球菌的新型粘膜疫苗平台，可刺激对金黄色葡萄球菌的全身和粘膜免疫反应。

大多数病原体通过粘膜引发感染，因此将疫苗直接递送至粘膜可能有利于刺激进入部位的保护性免疫。PilVax 是一种新型粘膜疫苗平台，它利用乳酸乳球菌细菌在菌毛内稳定表达疫苗肽抗原的多个拷贝，从细胞壁延伸的毛发状结构。这种策略在鼻内免疫后引发了对模型抗原的全身和粘膜抗体反应，但尚未测试其刺激保护性粘膜免疫的能力。来自金黄色葡萄球菌的纤连蛋白结合蛋白 A 的充分表征的线性 B 细胞表位 D3(22-33) 被成功引入 PilVax 并通过鼻内递送给小鼠。在接种疫苗的小鼠的血清和呼吸道粘膜中检测到特异性抗肽免疫球蛋白 (Ig) G 和 IgA 抗体。还评估了对主要菌毛骨架蛋白 Spy0128 的反应；在全身以及呼吸道和肠粘膜中都产生了针对该抗原的强烈抗体反应。用小鼠适应的金黄色葡萄球菌 JSNZ 菌株鼻内攻击小鼠，并在攻击后 7 天量化金黄色葡萄球菌的负荷。出乎意料的是，与未接种疫苗的对照小鼠相比，无论是否存在肽，暴露于 PilVax 都会导致肠道和鼻粘膜中金黄色葡萄球菌的负荷显着降低（均 P < 0.05）。保护机制不明确，

更新日期：2020-03-09

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