# LETHAL BACTEREMIA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1987 · $267,508

## Abstract

Human antiserum against E. coli J5, a mutant strain whose endotoxin (LPS)
contains core determinants common to all gram-negative bacteria but lacks
serotype-specific oligosaccharide, protects patients from shock and death
due to gram-negative bacteremia.  The antitoxic effect of passive J5
immunization has been demonstrated not only in treatment of established
bacteremia but also when prophylactic antiserum is administered frequently
to patients at high risk of fatal endotoxin shock because of trauma or
abdominal surgery.  Recent construction of a stable human-mouse
heteromyeloma cell line has allowed us to make hybridomas producing human
anti-J5 LPS monoclonal antibodies (mAb).  One of these, an IgM, binds to a
wide variety of gram-negative bacteria and their lipopolysaccharides and
prevents the dermal Shwartzman reaction and death from experimental E.
coli, Klebsiella and Pseudomonas bacteremia.  Such mAb's offer not only
unlimited production of safe immunotherapeutic agents but also the chance
to probe LPS antigenic relatedness and mechanisms of LPS biologic
activities with new precision.  We plan to use our heteromyelomas to
generate a library of human anti LPS core monoclonal antibodies which are
diverse with respect to isotype, epitope specificity and binding
characteristics.  We will attempt fusions with splenocytes and peripheral B
cells sensitized in vitro as well as in vivo.  Then we will use these
antibodies to pursue six Specific Aims:  1) To correlate epitope
specificity with the extent of cross-reactivity between J5 LPS and the core
determinants (core sugars + lipid A) of endotoxins from clinical
gram-negative isolates; 2) To dissect the mechanisms by which LIPS core
antibody protects against LPS and infection; 3) To study whether epitope
specificity is a significant determinant of LPS biologic activities such as
mitogenicity, complement activation and pyrogenicity; 4) To raise rodent
anti-idio-type antibodies against LPS mAb's and to see if any of them mimic
LPS; 5) To adapt human hybridomas to growth in serum-free media; and 6) To
explore the possibility of preserving antibody production permanently by
cloning J5 Immunoglobulin genes.  We have sufficient preliminary data in
most of these areas to encourage us that substantial progress can be made
toward our long-term goals of undertanding the pathogenesis of endotoxin
shock and providing a safe, stable source of protective anti-LPS antibody
to prevent the toxic consequences of gram-negative bacteremia in patients.

## Key facts

- **NIH application ID:** 3124658
- **Project number:** 5R01AI010108-17
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** ELIZABETH J. ZIEGLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $267,508
- **Award type:** 5
- **Project period:** 1978-01-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124658

## Citation

> US National Institutes of Health, RePORTER application 3124658, LETHAL BACTEREMIA (5R01AI010108-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124658. Licensed CC0.

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