Mortensen Rasmus, Christensen Dennis, Hansen Lasse Bøllehuus, Christensen Jan Pravsgaard, Andersen Peter, Dietrich Jes
Statens Serum Institut, Department of Infectious Disease Immunology, Copenhagen, Denmark.
University of Copenhagen, Department of Immunology and Microbiology, Copenhagen, Denmark.
PLoS One. 2017 Apr 17;12(4):e0175707. doi: 10.1371/journal.pone.0175707. eCollection 2017.
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（A组链球菌，GAS）可引发多种感染。通过飞沫进行呼吸道传播是最常见的传播方式，但它也可能通过其他途径感染宿主，如皮肤损伤。因此，为推动未来抗GAS疫苗的研发，研究保护性免疫与疫苗接种途径之间的关系至关重要。为探究这一点，我们研究了经肠胃外途径接种的抗GAS疫苗能否预防鼻内GAS感染，或者这是否需要局部启动的免疫。我们发现，尽管经肠胃外途径接种的CAF01佐剂GAS疫苗能诱导强大的全身性Th1/Th17/IgG免疫，有效预防腹腔内GAS感染，但对鼻内感染却没有保护作用。然而，在小鼠攻毒模型中，经鼻内途径接种相同疫苗能够诱导针对反复鼻内GAS感染的保护作用。经肠胃外途径接种的疫苗缺乏鼻内保护作用，这与感染部位黏膜回忆反应减弱有关。综上所述，我们的结果表明，局部启动的免疫对于抵御化脓性链球菌鼻内感染至关重要。
