Allergens conjugated with several simple repeating
polymers have reduced allergenicity in man, but large doses retain the ability to suppress ongoing
allergen-specific
IgE synthesis in strains of high-responder mice. To determine whether suppression of
IgE antibodies could be induced in man, preliminary trials of immunologic responses to conjugates in man were carried out in ragweed
hay fever patients treated with
antigen E (AgE) coupled to methoxypolyethylene
glycols ( MPEGs ) of 5000 and 2000 daltons, lauryloxypolyethylene glycol of 1200 daltons, and a random copolymer of D-
lysine and D-
glutamic acid of 69,000 daltons. In varying degrees all these conjugates had reduced allergenicity by basophil histamine release when these conjugates were compared with native AgE and could suppress
IgE response in mice. Patients received one of these conjugates or native AgE in a series of
subcutaneous injections and were observed for
allergic reactions. The conjugates induced a lower rate of systemic reaction than native AgE but failed to induce early suppression of
IgE antibodies. Instead, early rises in
IgE antibody occurred in the several groups and were followed by a slow decline during a year or more that was similar to that observed with standard
immunotherapy. Because the conjugates eventually caused local and systemic
allergic reactions as the dose was raised, it was not possible to test the
IgE-suppressive effects at doses similar to those used in mice. In contrast, rapid sustained rises in
IgG antibodies occurred in all groups. The
MPEG conjugates appeared to be more effective than native AgE in this regard. The reduced rate of systemic reaction and rapid rise in
IgG antibody that was noted with
MPEG conjugates make them worth further exploration as agents for
immunotherapy.