TY - JOUR
T1 - Heptavalent O-Antigen Bioconjugate Vaccine Exhibiting Differential Functional Antibody Responses Against Diverse Klebsiella pneumoniae Isolates
AU - Wantuch, Paeton L.
AU - Knoot, Cory J.
AU - Robinson, Lloyd S.
AU - Vinogradov, Evgeny
AU - Scott, Nichollas E.
AU - Harding, Christian M.
AU - Rosen, David A.
N1 - Publisher Copyright:
© 2024 The Author(s).
PY - 2024/9/15
Y1 - 2024/9/15
N2 - Klebsiella pneumoniae is the leading cause of neonatal sepsis and is increasingly difficult to treat owing to antibiotic resistance. Vaccination represents a tractable approach to combat this resistant bacterium; however, there is currently not a licensed vaccine. Surface polysaccharides, including O-antigens of lipopolysaccharide, have long been attractive candidates for vaccine inclusion. Herein we describe the generation of a bioconjugate vaccine targeting 7 predominant O-antigen subtypes in K. pneumoniae. Each bioconjugate was immunogenic in isolation, with limited cross-reactivity among subtypes. Vaccine-induced antibodies demonstrated varying degrees of binding to a wide variety of K. pneumoniae strains. Furthermore, serum from vaccinated mice induced complement-mediated killing of many of these strains. Finally, increased capsule interfered with the ability of O-antigen antibodies to bind and mediate killing of some K. pneumoniae strains. Taken together, these data indicate that this novel heptavalent O-antigen bioconjugate vaccine formulation exhibits limited efficacy against some, but not all, K. pneumoniae isolates.
AB - Klebsiella pneumoniae is the leading cause of neonatal sepsis and is increasingly difficult to treat owing to antibiotic resistance. Vaccination represents a tractable approach to combat this resistant bacterium; however, there is currently not a licensed vaccine. Surface polysaccharides, including O-antigens of lipopolysaccharide, have long been attractive candidates for vaccine inclusion. Herein we describe the generation of a bioconjugate vaccine targeting 7 predominant O-antigen subtypes in K. pneumoniae. Each bioconjugate was immunogenic in isolation, with limited cross-reactivity among subtypes. Vaccine-induced antibodies demonstrated varying degrees of binding to a wide variety of K. pneumoniae strains. Furthermore, serum from vaccinated mice induced complement-mediated killing of many of these strains. Finally, increased capsule interfered with the ability of O-antigen antibodies to bind and mediate killing of some K. pneumoniae strains. Taken together, these data indicate that this novel heptavalent O-antigen bioconjugate vaccine formulation exhibits limited efficacy against some, but not all, K. pneumoniae isolates.
KW - bioconjugation
KW - capsular polysaccharide
KW - Klebsiella pneumoniae
KW - O-antigen polysaccharide
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85194413685&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiae097
DO - 10.1093/infdis/jiae097
M3 - Article
C2 - 38401891
AN - SCOPUS:85194413685
SN - 0022-1899
VL - 230
SP - 578
EP - 589
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -