IgE and IgG Antibodies to  -Propiolactone and Human Serum Albumin Associated with Urticarial Reactions to Rabies Vaccine

Abstract

We examined the antibody response to a rabies vaccine doubly inactivated with 0.025% beta-propiolactone and 0.1% tri(n)butyl phosphate and stabilized with 2.5% human serum albumin. Antibodies were measured by using the following four antigen preparations: complete doubly inactivated rabies vaccine, rabies vaccine inactivated only with tri(n)butyl phosphate, beta-propiolactone and human serum albumin, and human serum albumin alone. The fluid phase of the preparation of beta-propiolactone and human serum albumin completely inhibited IgE binding to solid-phase vaccine. Of 21 subjects with urticarial reactions to a booster, 19 had IgE to doubly inactivated vaccine and to beta-propiolactone and human serum albumin. None of 27 immunized subjects without urticaria had detectable IgE. In paired pre- and postimmunization sera, IgE appeared in six of seven of the subjects with urticaria and in one of seven nonreactors. These sera did not contain a significant level of IgE to singly inactivated vaccine or to human serum albumin alone.

Fixation of penicilloyl groups to albumin and appearance of anti-penicilloyl antibodies in penicillin-treated patients.

“…This observation agrees with previous results (25,26). A similar observation notes the derivatization of albumin by the fi propiolactone used in the rabies vaccine, resulting in a component that is seemingly antigenic in human (27). The high frequency of antibody response is probably related to protracted persistence of penicilloylated albumin.…”

Development of a new hydrogen peroxide–based vaccine platform

“…This was also associated with an inadequate antiviral antibody response, linked to formaldehyde-induced alteration of the measles hemolysin (F protein) 6 . Inactivation of viruses with BPL may also trigger adverse immune reactions, including the induction of allergic responses through chemical modifications of vaccine components 7,8 . It is unclear whether this was a factor in a recent phase 1 clinical trial in which one of 20 subjects developed urticaria shortly after booster vaccination with a 4.8-μg dose of BPL-inactivated yellow fever vaccine 9 .…”

Les réactions allergiques et pseudo-allergiques aux vaccins

“…Des réactions diverses sont observées chez 15 % des patients immunisés par les vaccins antirabiques. Grâce à un RAST artisanal, une HSI à la bêtapropionolactone a été diagnostiquée chez quelques patients [55].…”