Work

A capsule-deficient Klebsiella pneumoniae strain reveals its O-polysaccharide as a potent immunomodulatory and protective vaccine antigen

Year: 2026

Type: article

Abstract: Klebsiella pneumoniae (KP), particularly hypervirulent (hvKP) and multidrug-resistant strains (e.g., Carbapenem-resistant KP, CRKP), poses a severe threat to human and animal health, underscoring the urgent need for effective vaccines. KP possesses over 80 distinct K (capsular) antigens, complicating vaccine design. In contrast, its O-antigens (only 11 types) are more concentrated, with the vast majority of clinical isolates belonging to serotypes O1, O2, O3 or O4, offering greater potential for broad coverage. Predominant hvKP serotypes K1 and K2 both contain the O1 antigen, making it a strategic target. This study utilized a capsule-deficient mutant, K7R R (hypothesized to overproduce O1 antigen), to explore the immunological properties of its polysaccharide fractions. The extracellular polysaccharide (EPS) rapidly activated the MAPK pathway (p-p38) in RAW264.7 cells and stimulated the release of IL-1β, IL-6, TNF-α, and IFN-γ, indicating immunomodulatory activity. Purification of EPS yielded two galactose-enriched polysaccharide fractions: OPS 1 (high molecular weight) and OPS 2 (low molecular weight, major component). Both fractions were specifically recognized by an O1-antiserum and capable of inducing proinflammatory cytokine responses. Mouse immunization showed that EPS and OPS 1 induced high antibody titers (~1:3.5×10 5 and ~1:1.1×10 5 , respectively), whereas OPS 2 induced markedly lower titers (~1×10 3 ). In acute pneumonia models challenged with KP26 (K1:O1) and K7 (K2:O1), EPS immunization provided the highest protection (60% survival), with OPS 1 conferring better efficacy than OPS 2 . Immunized groups also exhibited obviously reduced lung pathology and cytokine levels compared to controls. In conclusion, these results demonstrate that K7R R -derived EPS, particularly the high molecular weight OPS 1 -represent promising vaccine antigen candidates against KP serotypes K1 and K2. The high O-polysaccharide yield of K7R R further emphasizes its utility for developing efficient and cost-effective vaccines against K. pneumoniae infections.

Source: Animals and zoonoses.

DOI: 10.1016/j.azn.2026.04.002