# GENETIC CONTROL OF ANTIBODY RESPONSES TO POLYSACCHARIDES

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1991 · $232,451

## Abstract

The long term objective of this proposal is to increase our
understanding of immune responses to polysaccharide antigens. To
accomplish this goal, we will measure serum antibody responses to
bacterial PS vaccines, and in vitro Ig production by mitogen
stimulated lymphocytes from normal and abnormal subjects.  In Aim
1, we will investigate the immunologic and genetic basis of
"vaccine failure" in patients who develop Haemophilus influenzae
type b (Hib) disease despite previous vaccination with Hib
polysaccharide (PS) vaccine.  This group previously has been shown
to have impaired serum antibody responses to Hib PS despite having
normal concentrations of serum Ig.  The techniques we propose to
use to evaluate these patients include:  a. measurement of their
IgM, IgG and IgG subclass-specific antibody responses to
immunization with different bacterial PS antigens presented as
isolated PS vaccine (T-independent) or as a covalent PS-protein
conjugate (T-dependent); b. measurement of their IgG antibody
responses to Hib outer membrane proteins following recovery from
Hib disease; c. measurement of Ig secretion in vitro by mitogen-
stimulated lymphocytes; and d. determination of the frequencies of
different allotype haplotypes previously associated with altered
risk of Hib PS vaccine failure.  The results of these studies will
define the range of the immunologic deficits present in these
children, and the extent to which genes in linkage disequilibrium
with Ig allotypes contribute to vaccine failure.  In Aim 2, we will
immunize healthy adults with meningococcal A and C PS and tetanus
toxoid vaccines and compare their respective IgG2 antibody
responses in relation to G2m(23) allotype status to determine
whether the relationship observed previously in normal individuals
between this allotype and the magnitude of the IgG2 antibody
responses to Hib PS is specific or extends to IgG2 responses to
other PS antigens or to protein antigens. We also will compare the
amount of IgG2 produced in vitro by mitogen-stimulated lymphocytes
from G2m(23)-positive and negative subjects in an effort to develop
an in vitro assay to investigate T and B cell interactions
contributing to this allotype association.  Finally, in Aim 3, we
will compare the relative bactericidal and opsonic activities of
IgG1, IgG2 and IgG3 antibodies to Hib PS.  Our previous data
suggest that genetic factor as well as age of immunization and type
of vaccine influence the IgG subclass distribution of serum
antibody to Hib PS.  The results of these studies will indicate
whether individuals with similar levels of total IgG antibody but
different subclass distributions are equally protected against Hib
disease.

## Key facts

- **NIH application ID:** 3127567
- **Project number:** 5R01AI017962-10
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** Dan M. Granoff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $232,451
- **Award type:** 5
- **Project period:** 1981-07-01 → 1993-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127567

## Citation

> US National Institutes of Health, RePORTER application 3127567, GENETIC CONTROL OF ANTIBODY RESPONSES TO POLYSACCHARIDES (5R01AI017962-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127567. Licensed CC0.

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