Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.化脓性链球菌（Streptococcus pyogenes，A群链球菌，GAS）可引发多种感染性疾病。经飞沫传播的呼吸道途径是其最常见的感染方式，但该菌也可通过皮肤破损等其他途径感染宿主。为推动未来抗GAS疫苗的研发，探究保护性免疫与疫苗接种途径之间的关联至关重要。为探究这一问题，本研究考察了经肠外接种的抗GAS疫苗能否抵御鼻内GAS感染，或是此类感染是否需要局部预致敏免疫应答才能被有效防控。研究发现，经CAF01佐剂化的肠外接种GAS疫苗，虽可诱导强烈的全身性Th1/Th17/IgG免疫应答，能够有效抵御腹腔内GAS感染，但无法为鼻内感染提供保护。然而，通过鼻内途径接种的同款疫苗，则可在小鼠攻毒模型中诱导出抵御反复鼻内GAS感染的保护效力。肠外接种疫苗无法引发鼻内保护的现象，与感染部位的黏膜回忆应答减弱存在相关性。综上，本研究结果证实，局部预致敏免疫应答对于抵御化脓性链球菌的鼻内感染具有重要意义。