New Biological Insights in the Immunomodulatory Effects of Mucosal Polybacterial Vaccines in Clinical Practice

Abstract

A main focus in healthcare is the active search for alternative strategies to antibiotics, both for prophylactic and therapeutical interventions, due to the accelerated and widespread increase in antibiotic resistance. This problem is more marked for patients with recurrent infections, in which the risk for antibiotic resistance and adverse effects is higher and can be life-threatening. Although antibiotics remain the mainstay of treatment for infectious diseases, prophylactic vaccines via the mucosal route in defined populations of patients with recurrent infections has gained use in recent years. Concomitantly, relevant advances in the formulation and administration of these vaccines driven by an increased knowledge of mucosal immunity have expanded their use, although still in its infancy. These drugs target both the innate and adaptive immune systems, at the actual point of entry of most pathogens. A fascinating new application of the concepts of trained immunity may open novel studies in their potential uses, given the paradoxically simultaneous pro-tolerogenic and boosting effector effects on diverse immune cells for different antigens. Here we delineate an updated review on the immunomodulatory mechanisms of mucosal polybacterial vaccines.

Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells

“…Preclinical studies were also reported for several novel immunomodulators. TLR7 ligands coupled to allergens, probiotics, microbial products, heat‐killed bacterial strains, or polybaterial preparations showed efficacy in mouse models of allergic airway inflammation …”

“…TLR7 ligands coupled to allergens, probiotics, microbial products, heat-killed bacterial strains, or polybaterial preparations showed efficacy in mouse models of allergic airway inflammation. [220][221][222][223] Different types of fusion proteins that conjugate allergens to different carriers such as Fcγ fragments, 224 bacterial S layer proteins, 225 TLR5-ligand flagellin, 226 or grass or cat pollen peptides fused to an immunogenic carrier from hepatitis B virus (BM32) 227 have been developed and assessed in different preclinical models. In humans, until present, only few vectors administered via parenteral route have been studied.…”

Human dendritic cells activated with MV130 induce Th1, Th17 and IL‐10 responses via RIPK2 and MyD88 signalling pathways

“…There is an urgent need for new alternative approaches to antibiotics for the prevention and treatment of RRTIs. Different types of mucosal bacterial vaccines have received a lot of attention over the last years as they significantly reduce the rate of infections in RRTIs patients [3,4,[12][13][14]. Bacterial vaccines containing soluble antigens (bacterial lysates) administered through the oral route were initially used to treat and prevent RRTIs [3,12,15,16].…”

“…Different types of mucosal bacterial vaccines have received a lot of attention over the last years as they significantly reduce the rate of infections in RRTIs patients [3,4,[12][13][14]. Bacterial vaccines containing soluble antigens (bacterial lysates) administered through the oral route were initially used to treat and prevent RRTIs [3,12,15,16]. More recently, polybacterial preparations (PBP) based on whole inactivated components and delivered through the sublingual route have been also studied as novel alternatives [3,14].…”

Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

“…Mucosal immunization with BCG has been investigated. The total mucosal surface area is about 200 times larger than skin, and vaccination at the sites of pathogen invasion could generate a protective immunological response [46]. While oral BCG was the initial delivery method almost a century ago, oral vaccines generally must survive the acidic environment of the stomach and run the risk of generating tolerance without an adjuvant [47].…”