Sublingual therapeutic immunization with a polyvalent bacterial preparation in patients with recurrent respiratory infections: immunomodulatory effect on antigen-specific memory CD4+ T cells and impact on clinical outcome

Abstract

cells specific to Bactek® antigens at month 6 in comparison to baseline (P < 0·0001). A significant increase in total CD3+ T cells was also observed (P < 0·05). No significant differences were observed between baseline and month 6 in levels of total immunoglobulins, specific antibodies and B, T or NK cell subsets. A significant reduction in the patient's rate of RRTIs was observed compared with 1 year prior to initiation of therapy (P < 0·0001). The results demonstrate that long-term administration of a sublingual polyvalent bacterial preparation in patients with RRTIs exerts an immune stimulating effect on CD4 + T helper cell responses to bacterial antigens which could be associated with clinical benefit.

Evaluation of a therapeutic vaccine for the prevention of recurrent urinary tract infections versus prophylactic treatment with antibiotics

“…However, sublingual and nasal mucosa can serve as an inductive site for generating a broad spectrum of mucosal and systemic immune responses, including also the respiratory and genitourinary tracts [24, 28] with a high degree of efficacy and persistence of the immune response [29]. Sublingual administration of immunogens such as cholera toxin and ovalbumin induces systemic humoral dose-dependent immune responses [28], mucosal antibody responses [28], and an immune-stimulating effect on CD4+ T helper cell responses to bacteria [30]. …”

“…This observation highlights the need for a more prolonged treatment or for starting a new period of 3-month treatment. In a pilot trial using a similar immunostimulant, with a different bacterial composition because it focused on preventing recurrent respiratory tract infections, the treatment period was of 6 months’ duration and had a clinical effect for a minimum period of 12 months [30]. …”

Animal Models of Immunity to Female Genital Tract Infections and Vaccine Development

“…Our own studies show that SLI with rMOMP and CTA1-DD protects mice against hydrosalpinx and oviduct inflammation (O'Meara et al, 2014). Clinical trials of SLI with Bactek ® , a polyvalent bacterial vaccine, was well tolerated in patients and reduced the incidence of recurrent respiratory infections (Alecsandru et al, 2011), and sublingual delivery of allergens to induce tolerance and reduce allergies (sublingual immunotherapy; Passalacqua and Canonica, 2011;Passalacqua et al, 2013) is also well accepted in humans. Collectively, these data suggest that SLI is safe in humans and able to target multiple mucosal sites, including the genital tract.…”

Technologies to Improve Immunization

“…Live virus or bacterial vac-tions are the major focus of published clinical trials for oral mucosal vaccination. [580][581][582][583] There are few clinical data on traditional prophylactic vaccines delivered via the SL or buccal route, although studies are registered on ClinicalTrials.gov for influenza, cholera, and HPV. 584,585 Preclinical studies of SL vaccines have demonstrated immunogenicity in mice using viral vectors such as adenovirus-based vaccines [586][587][588] and bacterial vectors such as Bacillus subtilis.…”