Klebsiella pneumoniae bioconjugate vaccine functional durability in mice
Paeton L Wantuch1, Cory J Knoot2, Emily C Marino3
1Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
Klebsiella pneumoniae is a leading cause of hospital-acquired infections as well as the leading cause of neonatal sepsis worldwide. Further, increasing antibiotic resistance in this pathogen makes K. pneumoniae troublesome to treat. Despite its clinical importance, there is not yet an approved K. pneumoniae vaccine available. Here we tested antibody durability and long-term functionality of two previously reported bioconjugate vaccines targeting the K. pneumoniae capsular type K2 and O-antigen type O1v1. We demonstrate that both antibodies are durable in mice for up to six months with significant IgG titers. However, only the K2 antibodies exhibit functionality out to six months as evidenced by serum bactericidal activity and survival in a murine bacteremia challenge model. These results are another promising step towards demonstrating the clinical capacity of bioconjugate vaccines and their induction of durable antibody responses.
Insights
This study evaluated the long-term effectiveness of two Klebsiella pneumoniae (K. pneumoniae) bioconjugate vaccines in mice. While antibodies remained durable for six months, only K2 antibodies showed sustained functionality, offering a promising step for vaccine development.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Klebsiella pneumoniae is a major cause of hospital-acquired infections and neonatal sepsis globally.
- Increasing antibiotic resistance in K. pneumoniae complicates treatment options.
- No K. pneumoniae vaccine is currently approved for clinical use.
Purpose of the Study:
- To assess the durability and long-term functionality of antibodies induced by two K. pneumoniae bioconjugate vaccines.
- To evaluate the potential of bioconjugate vaccines in eliciting sustained protective immune responses against K. pneumoniae.
Main Methods:
- Testing antibody durability and functionality in mice up to six months post-vaccination.
- Measuring IgG titers and assessing serum bactericidal activity.
- Evaluating survival rates in a murine bacteremia challenge model.
Main Results:
- Both vaccine candidates induced durable antibodies in mice for six months, maintaining significant IgG titers.
- Antibodies targeting K. pneumoniae capsular type K2 demonstrated sustained functionality.
- K2 antibodies showed significant serum bactericidal activity and improved survival in a challenge model.
Conclusions:
- Bioconjugate vaccines can induce durable antibody responses against K. pneumoniae.
- Sustained antibody functionality is crucial for long-term protection.
- These findings support the potential of bioconjugate vaccines for clinical application against K. pneumoniae infections.
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