# ANTIBODY TO H. INFLUENZAE CAPSULAR POLYSACCHARIDE

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1989 · $161,636

## Abstract

Haemophilus influenzae b (Hib) is the most common cause of meningitis and
childhood sepsis in the US.  The capsular polysaccharide (CP) is a major
virulence factor of Hib.  Vaccines composed of the purified CP prevent Hib
disease in children older than l8 mo., but have proven poorly immunogenic
in infants, the age-group with the highest attack rate.  The delayed
ontogeny of the antibody (Ab) response to the Hib CP in man may mimic the
delayed ontogeny of the response to certain polysaccharides in mice.  In
addition to being delayed in ontogeny, the murine Ab response to certain
polysaccharides is restricted in diversity and expresses cross-reactive
idiotypes (IdX) that are found on a high proportion of Ab molecules in most
individuals of a strain.  We have found that the human Ab response to the
Hib CP is also highly limited in diversity, with restriction in light chain
type and Ab charge heterogeneity as detected on isoelectric focusing (IEF)
gels.  The limited diversity, the finding of identical Ab IEF patterns in
unrelated individuals, and the ability to immunize older humans to induce
high levels of an Ab that is directed to a clinically relevant antigen,
makes it possible to define the structural basis, regulation, and ontogeny
of the diversity of the human anti-Hib CP Ab response.

The aims of the proposed research are to:  l) determine the relative
contribution of the Ab light (L) and heavy (H) chains to human Ab diversity
and to binding of the Hib CP.  Both human serum and hybridoma Ab will be
prepared and purified.  The L and H chains will be isolated and we will
determine L chain charge heterogeneity by IEF, L and H chain subgroups by
amino acid sequencing, and L and H chain contribution to antigen binding;
2) define the existence of IdX and its molecular basis by amino acid
sequencing; 3) define the molecular basis of the Ab repertoire by amino
acid sequencing; 4) determine the relative protective capacity of Ab with
different V-regions using an animal model of the Hib disease; 5) define the
normal ontogeny of Ab V-region expression and determine whether it is
altered by passive immunization of the infant with Ab through maternal
immunization or by active immunization with the Hib CP linked to a protein
carrier; 6) determine whether autologous anit-idiotypic Ab is produced
after immunization; and 7) determine whether Ab V-region expression is
inherited and linked to immunoglobulin allotype markers.  The long-range
goal will be to apply the knowledge acquired of Ab V-region structure and
regulation to develop an effective vaccine strategy to prevent Hib disease
in man.

## Key facts

- **NIH application ID:** 3127034
- **Project number:** 5R01AI017217-08
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** Richard A. Insel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $161,636
- **Award type:** 5
- **Project period:** 1980-09-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127034

## Citation

> US National Institutes of Health, RePORTER application 3127034, ANTIBODY TO H. INFLUENZAE CAPSULAR POLYSACCHARIDE (5R01AI017217-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127034. Licensed CC0.

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