Protection conferred by mucosal novel bivalent Klebsiella pneumoniae vaccine immunization associates with presence of lung CD4+ TRM.

Abstract

Klebsiella pneumoniae is the principal cause of hospital-acquired infection with a high morbidity and mortality in immunocompromised individuals, yet no vaccine is approved. Here, we developed a novel bivalent subunit vaccine for the prevention of K. pneumoniae infection based on the outer membrane protein GlnH and the fimbriae protein FimA. The survival rate of immunized mice was significantly increased compared to that of unimmunized mice, while the bacterial burden, weight loss, and lung pathology were drastically reduced. Furthermore, vaccine-elicited CD4⁺ T_RM cells were observed in lung tissues and appeared to play a critical role in vaccine efficacy. Transcriptomic analysis of total lung tissues from mice treated by FTY720 (S1PR1 inhibitor that blocks lymphocyte egress from secondary lymphoid structures) showed that cell activation, cytokine secretion and enhancement of the killing ability of neutrophils were related to the mechanism of protection against K. pneumoniae infection. These findings indicate that GlnH and FimA are effective candidate bivalent vaccine to fight K. pneumoniae infection.