Allergoid

Abstract: Summary.Thehighly purified majorallergenic component ofryegrass pollen (GroupI)wasusedtoinvestigate thepossibility ofdestroying selectively the allergenic properties ofanantigen, whilelargely retaining itsoriginal immunizingcapacities. Theallergen wastreated undermildconditions withformalin alone orformalin plus areactive lowmolecular weight additive. Certain derivatives (allergoids) showedwellover99percentreduction inallergenicity, determinedbythehistamine released fromallergic humanleucocytes invitro, butwere still abletocombine withrabbit antibody against native antigen. Furthermore, theallergoids stimulated production (inguinea-pigs) ofappreciable amountsof antibody abletoinhibit native allergen-mediated humanallergic histamine release invitro andtocross-react withnative antigen byPCA tests innormal guinea-pigs. Residual allergenicity andcross-immunogenicity (bytheinhibition assay) ofthe different formalinized derivatives varied appreciably according totheadditive used informalinization, butthecross-reactivities ofthedifferent preparations in quantitative precipitin analysis against rabbit anti-native antigen serumwere similar. Theresidual allergenicities ofindividual derivatives varied byup to 1000-fold indifferent cell preparations, suggesting aheterogeneity ofallergenic determinants. Allergoid derivatives showednohapten-like activity inthatthey wereunabletoinhibit allergen-mediated histamine release fromleucocytes. Thetheoretical andpractical application ofallergoids isdiscussed, including their potential usefulness inimproving theimmunotheraphy ofatopic humans.

Abstract: Specific immunotherapy is still widely used in grass-pollen allergy, but its side effects may limit its use. We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind, placebo-controlled study. Eighteen patients received placebo, 19 received the low-dose schedule (maximal dose: 2000 PNU) and 20 received the high-dose schedule (maximal dose: 10,000 PNU). Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU. Before the onset of the pollen season, patients had a nasal challenge with orchard grass-pollen grains, a skin test titration, and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo. Symptoms and medications for rhinitis and asthma were studied during the season, and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms. There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges. High-molecular-weight allergoids are safe and effective.

Abstract: Background: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. Methods: We randomly assigned 24 children allergic to grass pollen to receivelocal allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. Results: The active-treatment group had a statistically significant reduction of total symptoms (P<0.05), especially bronchial symptoms (P<0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EG1 increased significantly only in the placebo group during natural allergen exposure (P<0.01). Conclusions: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.

Abstract: Background: Sublingual immunotherapy (SLIT) appears to be acceptably safe in clinical trials, but post-marketing data are needed to provide essential information. This study specifically evaluated the safety of commercial SLIT in adult patients in a post-marketing phase. Methods: A total of 198 patients (83 male, 115 female, mean age 24.4 years) receiving SLIT for respiratory allergy were followed up for 3 years by a specific questionnaire for side-effects. SLIT (LAIS, Lofarma SpA, Milan, Italy), a monomeric allergoid in tablets, was administered, in association with drug therapy, pre- or pre-coseasonally for pollen and continuously for mites. The average duration was 12‐36 months, and the total of doses was about 32 800. Side-effects were grouped as ocular, gastrointestinal, rhinitis, asthma, urticaria, edema of tongue/lips, and anaphylaxis. The severity was graded as low (no need for treatment or dose adjusting, no interference with activities), moderate (interference with activities/need for drugs/SLIT discontinuation), and severe (life-threatening/hospitalization/emergency care). Results: Seventeen events corresponding to 7.5% of patients and 0.52 per 1000 doses were reported. Seven episodes of rhinitis (two in two patients), three of oral itching, and one of abdominal pain were self-limiting. Two cases of urticaria and two of abdominal pain/nausea were controlled by a temporary dose-adjustment, and one case of urticaria and conjunctivitis required oral antihistamines. Medical intervention was needed in six patients only during a 3-year period. Conclusions: The results of this study, performed in a real situation of clinical practice, confirm the satisfactory safety profile of SLIT.