# BIOLOGY AND IMMUNOLOGY OF GRAM-NEGATIVE BACILLI

> **NIH NIH R01** · BOSTON CITY HOSPITAL · 1988 · $179,020

## Abstract

These investigations examine possible enhancement of resistance to
Gram-negative bacillary infections by immunization with antigens shared by
most Enterobacteriaceae and Pseudomonadaceae.  Active and passive
immunization with an antigen present in the basal, core portion of
lipopolysaccharide (LPS) (Re mutant of S. minnesota) have been shown to
induce significant protection against lethal challenge with heterologous
bacilli and LPS.  Similarly, patients with high titers of antibody to the
Re mutant at the onset of bacteremia experienced shock and a fatal outcome
only 1/3 as often as those with low titers.  Field trials by others have
demonstrated that administration of human antisera against the J5 mutant
(Rc chemotype) of E. coli was associated with a 2-fold reduction in
fatality in Gram-negative bacteremia.  Immunization of volunteers with
preparations derived from Re and J5 mutants to develop vaccines for field
trials of the relative efficacy of antiserum to each mutant in the
treatment of bacteremia will be continued.  In addition, "modified
glycolipids", alone, and conjugated with polypeptides and proteins have
been prepared to develop component vaccines for induction of active rather
than passive protection.  "Modified glycolipids" have been shown to induce
earlier antibody titers and serum protective activity than whole cell
vaccines.  These have also been coupled with protein carriers and shown to
produce a "booster" or anamnestic response of antibody and protective
levels with substantial increase in IgG.  Previous studies have
demonstrated that protective activity after primary immunization, resides
chiefly with IgM antibody but recent studies have suggested that "booster"
doses of "modified glycolipid" and conjugated vaccines induce an anamnestic
response with IgG exerting the greatest protective activity.  Protective
IgG antibody would have considerable clinical and commercial utility
(easier, standardized methods of preparation and repeated courses of
volunteer immunization).  Studies with component vaccines are being
extended to evaluate their feasibility and safety.  Immunologic
cross-reactivity, already demonstrated between LPS and glycolipids of the
Re and J5 mutants, will be further evaluated to characterize the
immunodeterminant responsible for induction of protective antibody.  Mouse
monoclonal antibodies to both the Re and J5 mutants are being characterized
and several have been shown to protect against challenge with K. pneumoniae
and E. coli.  Similarly, human monoclonal antibodies have been prepared and
are being characterized.

## Key facts

- **NIH application ID:** 3125889
- **Project number:** 5R01AI014789-10
- **Recipient organization:** BOSTON CITY HOSPITAL
- **Principal Investigator:** WILLIAM R. MC CABE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $179,020
- **Award type:** 5
- **Project period:** 1977-09-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125889

## Citation

> US National Institutes of Health, RePORTER application 3125889, BIOLOGY AND IMMUNOLOGY OF GRAM-NEGATIVE BACILLI (5R01AI014789-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125889. Licensed CC0.

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