Induction of mycobacterial protective immunity by sublingual BCG vaccination.

Tuberculosis (TB) remains a tremendous global health problem, with 1/4 of the world's population infected and causing > 1 million deaths annually. Intradermal Bacillus Calmette-Guérin (BCG) vaccine given during infancy protects against severe forms of acute disease but does not prevent chronic infection or development of pulmonary TB. TB vaccine mucosal targeting potentially could induce mucosal resident immune cells with increased protective capacity against pulmonary infection and disease. Sublingual (SL) administration of vaccines may be an optimal mucosal delivery platform based on the high absorptive capacity of this mucosal surface, the extensive lymphoid tissue, and published preclinical studies demonstrating efficacy of SL vaccination against other pathogens. To this end, we performed preliminary testing of sublingual TB vaccines. Vaccination of mice with SL BCG elicited potent mycobacteria-specific T cell responses which persisted 16 weeks post-immunization. The magnitudes of the T cell responses were similarly induced after sublingual, intranasal, and subcutaneous BCG vaccination. Interestingly, serum mycobacteria-specific antibody responses and systemic recovery of BCG post-vaccination were lower after SL BCG compared with systemic BCG immunization. However, more importantly, SL BCG vaccinated mice were significantly protected against an aerosolized virulent M. tuberculosis challenge (P < 0.0001 compared to unvaccinated mice). Furthermore, this protection was long-lived, persisting for 16 weeks with >1 log CFU reduction compared with naïve challenged mice in both lungs and spleens (P < 0.0001 and P < 0.0028, respectively). These exciting results provide strong support for further studies exploring the mechanisms of protective immunity induced by sublingual BCG vaccination.

Inhalant allergy compounding the chronic vaginitis syndrome: characterization of sensitization patterns, comorbidities and responses to sublingual immunotherapy.

OBJECTIVE: To characterize sensitization patterns, diagnoses and comorbidities, and to assess the response of lower genital tract symptoms to sublingual immunotherapy for airborne allergens in a select population of patients with chronic vaginitis. METHODS: Fifty-two patients referred for allergy evaluation over a 44 month period were studied. Charts were retrospectively reviewed to establish: (1) gynecological diagnoses, (2) allergic-immunological diagnoses, and (3) IgE-mediated sensitivity to airborne allergens on presentation. Patients were contacted at 9-50 months of treatment to assess response to sublingual immunotherapy based on a questionnaire addressing frequency and severity of symptoms and use of medication to control symptoms. RESULTS: Recurrent vulvovaginal candidiasis was identified in 34 (65 %); vulvar vestibulitis syndrome in 12 (23 %); and contact dermatitis in 10 (19 %) patients. Comorbidities included: non-reflux gastrointestinal complaints in 11 (21 %), gastroesophageal reflux in 5 (9 %), migraines in 9 (17 %), chronic non-migrainous headaches in 8 (17 %), and chronic sinusitis in 6 patients (11 %). Asthma was diagnosed in 8 patients (15 %). Oral allergy syndrome was present in 6 (11 %). Most frequent sensitivities were to: ragweed in 33 (63 %), molds in 26 (50 %), dust mites in 23 (44 %), and grass in 12 (23 %) patients. Mono-sensitization was demonstrated for ragweed in 7 (13 %), and for molds, dust mites and grass for 3 (5 %) patients each. Candida sensitization was identified in 15 patients with chronic vaginitis (28 %). Eleven patients with recurrent vulvovaginal diagnosis (32 %) showed Candida sensitization. Response to immunotherapy was generally favorable with pruritus/irritation being more responsive than visceral pain. CONCLUSIONS: In a Midwestern referral population, chronic vaginitis compounded by inhalant allergy showed: (1) high incidence rate of recurrent vulvo-vaginal candidiasis, (2) Candida IgE-mediated sensitization in less than one-third of patients with recurrent vulvovaginal candidiasis, (3) comorbid conditions not dissimilar to those of other allergic patients, and (4) allergen sensitization pattern typical for the Midwest.

Comment on "therapeutic effects and biomarkers in sublingual immunotherapy: a review".

Numerous sublingual immunotherapy studies have shown efficacy using a wide variety of dosing regimens. Despite a few grade III and one anaphylactic reaction due to a patient over-dose, there have been no fatal reactions resulting from sublingual immunotherapy treatment. Although safer than SCIT, SLIT is still immunotherapy. Special consideration should be given to what will ensure the highest level of safety for the patient given his or her history, exam and allergy test results. Dosing levels for sublingual immunotherapy should be based on what is therapeutically effective for each individual patient and adjusted accordingly throughout the treatment course.

Quality of life improvement with sublingual immunotherapy: a prospective study of efficacy.

Due to its excellent safety profile, ease of administration, and economic considerations, sublingual immunotherapy (SLIT) is becoming a preferred form of allergen specific immunotherapy. The efficacy of SLIT is still debated. The purpose of this act of practice trial is to evaluate quality of life outcomes in patients treated with SLIT. Fifty one patients with allergic rhinoconjunctivitis demonstrated by skin testing completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation, at four months and at 10-12 months of SLIT. Significant improvement (P < 0.05) on six of seven domain categories of the RQLQ questionnaire was noted. Total RQLQ scores also showed significant improvement. This study supports SLIT as a modality effective in controlling allergic symptoms.

Emerging concepts of sublingual immunotherapy for allergy.

Allergen-specific immunotherapy is the only disease-modifying modality in the treatment of allergy. However, in spite of its validation by abundant experimental data and decades of clinical experience, subcutaneous immunotherapy has not become the mainstay treatment for allergy. The current concepts and methods of immunotherapy are examined with emphasis on the advantageous features of sublingual immunotherapy: cellular and molecular mechanisms are reviewed and the physiology of antigen presentation is discussed; effector cell activation is examined in order to address immunotherapy-precipitated reactions which may reflect on the efficacy of immunotherapy; and stability, dosing and delivery of allergen extracts are reviewed. It can be concluded that allergen-specific sublingual immunotherapy is a useful therapeutic modality which, with proper adjustments, is eligible for wide-scale application as therapy for allergy.

Local immunotherapy in allergy.

UNLABELLED: Specific immunotherapy is a very powerful tool which is currently underutilized in the treatment of allergies. Sublingual immunotherapy (SLIT) has many advantages over subcutaneous immunotherapy (SCIT), and has been well proven to work for many pollens and dust mites. Multiple studies have shown SLIT improves symptoms and reduces the reliance on medications. Sublingual treatment has been studied in Europe and is endorsed by the World Health Organization Committee on Immunotherapy as a viable alternative to SCIT. CONCLUSION: SLIT offers another option for patients who are not currently candidates for subcutaneous immunotherapy. Because of improved safety, convenience and compliance, sublingual immunotherapy should be used as a first-line treatment option.