# A capsule-based bioconjugate vaccine to prevent Klebsiella pneumoniae infections

> **NIH NIH R41** · VAXNEWMO, LLC · 2022 · $300,000

## Abstract

PROJECT SUMMARY
Klebsiella pneumoniae is an encapsulated human pathogen capable of causing a myriad of human infections.
Recently, K. pneumoniae has also emerged as one the most common causes of secondary bacterial pneumonia
in COVID-19 patients. Over the last 40 years, K. pneumoniae has evolved into two distinct pathotypes, known
as classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). cKp commonly acts as an
opportunistic pathogen causing disease in hospitalized or immunocompromised individuals. In fact, cKp is
annually responsible for 5% of all healthcare-associated infections and is the leading cause of nosocomial
pneumonia in the US. Furthermore, cKp isolates are often carbapenem-resistant (CR), limiting treatment options.
In the US, K. pneumoniae multilocus sequence type 258 (ST258) strains account for ~70% of all carbapenem-
resistant K. pneumoniae infections. Conversely, hvKp usually cause community-acquired infections in healthy
hosts that frequently manifest as community-acquired pneumonia. Like ST258 infections, hvKp infections have
high mortality rates approaching 40-60%. Currently, there are no licensed vaccines available to prevent K.
pneumoniae infections and none in clinical trials. Nevertheless, preliminary data demonstrate both cKp and hvKp
infections can be prevented by vaccines that target their capsular polysaccharide (CPS). Conjugate vaccines
consist of a CPS covalently attached to an immunogenic carrier protein. While the clinical benefits of conjugate
vaccines are well documented, the development of new conjugate vaccines targeting K. pneumoniae is lagging,
likely due to the high technological barriers to entry and high costs associated with conjugate vaccine production.
In addition, most conjugate vaccines are multivalent, further increasing manufacturing complexities. In order to
simplify conjugate vaccine production, we have developed an in vivo conjugation platform termed bioconjugation.
Bioconjugation allows for the simultaneous production of the CPS, the carrier protein and their subsequent
covalent linkage all within E. coli. Key to our bioconjugation platform is our patented conjugating enzyme, PglS,
which attaches virtually any polysaccharide to a unique amino acid sequence fused to the carrier protein.
Furthermore, bioconjugation is modular, allowing for rapid production of multiple, different CPS-protein
conjugates. Using our bioconjugation platform, we are developing a multivalent CPS-based bioconjugate vaccine
to prevent the majority of K. pneumoniae infections. In this Phase I STTR program, four serotypes were initially
selected (K1, K2, KL106, KL107) as these serotypes are associated with >80% of all hvKp (K1 and K2) isolates
worldwide and >70% of ST258 (KL106 and KL107) isolates in the US. In Aim 1, we will produce a tetravalent
(K1, K2, KL106, KL107) bioconjugate vaccine on a modified carrier protein glycosylated at an internal site, which
is expected to improve conjugate characteristics su...

## Key facts

- **NIH application ID:** 10379720
- **Project number:** 1R41AI167078-01
- **Recipient organization:** VAXNEWMO, LLC
- **Principal Investigator:** Christian Harding
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10379720

## Citation

> US National Institutes of Health, RePORTER application 10379720, A capsule-based bioconjugate vaccine to prevent Klebsiella pneumoniae infections (1R41AI167078-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10379720. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*