# SUPPRESSION OF ANTIBODIES BY TOLEROGENIC CONJUGATES

> **NIH NIH R01** · UNIVERSITY OF MANITOBA · 1988 · $78,828

## Abstract

Since common allergies are mediated primarily by IgE antibodies, the
objectives of the investigations are (i) the further elucidation of the
cellular mechanisms underlying the production of this class of antibodies,
and (ii) the synthesis of appropriate conjugates of monomethoxypolyethylene
glycol (mPEG) and polyvinyl alcohol (PVA), respectively, with allergens and
haptens, which are capable of specifically suppressing the formation of IgE
antibodies.  Such mPEG conjugates have been shown to abrogate the induction
of IgE and IgG antibodies if administered prior to sensitization, but to
enhance the production of IgG (i.e., blocking or protective) antibodies in
both allergic patients and animals if administered after sensitization.
Studies are proposed to unravel the cellular basis for this dual
immunological potential of mPEG conjugates which may reflect the
heterogeneity of different subpopulations of B cells with respect to their
state of differentiation and their reactivity with these conjugates.

As a result of the chemical modification of allergens by coupling to mPEG,
the products are safer for injection into patients in much higher doses
than conventional allergenic extracts.  The results of ongoing clinical
trials performed in different countries (under the aegis of Pharmacia AB of
Uppsala) are promising, in that the patients so treated appeared to have
fewer symptoms and required less medication.

The effectiveness of mouse monoclonal antibodies (MoAbs), which are being
increasingly used for diverse therapeutic purposes in man (in particular in
relation to organ transplantation, tumor localization and destruction) is
counteracted by their inherent immunogenicity.  Preliminary results in our
laboratory indicate that this complication can be overcome by pretreatment
of the recipients of MoAbs with mPEG conjugates of MoAbs.  The use of
tolerogenic mPEG conjugates is being also extended to include mPEG
derivatives of natural xenogeneic hormones or of diverse biologically
active factors synthesized by recombinant DNA technology, which are
immunogenic as has been demonstrated for human growth hormone (GH) and
insulin.  Studies have just been initiated in this laboratory for the
synthesis of tolerogenic conjugates of GH.

## Key facts

- **NIH application ID:** 3125781
- **Project number:** 5R01AI014526-11
- **Recipient organization:** UNIVERSITY OF MANITOBA
- **SAM.gov UEI:** KZVHNCYJMHJ3
- **Principal Investigator:** ALEC SEHON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $78,828
- **Award type:** 5
- **Project period:** 1978-01-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125781

## Citation

> US National Institutes of Health, RePORTER application 3125781, SUPPRESSION OF ANTIBODIES BY TOLEROGENIC CONJUGATES (5R01AI014526-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125781. Licensed CC0.

---

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