In a recent study published in Biotech, researchers examined bacterial mucosal vaccine vectors from 2015 to the present to identify a promising candidate for coronavirus 2 spike (S) protein (SARS-CoV-2). of severe acute respiratory syndrome or its fragments.
Study: Hacking commensal bacteria to consolidate the adaptive immune response of the mucosa to the intestinal-lung axis: future possibilities for protection against SARS-CoV-2. Image credit: PHOTOCREO Michal Bednarek / Shutterstock
Fund
A better understanding of the interaction between host and commensal bacteria in mucosal niches and specific host immunoregulatory pathways could help expand the target repertoire in reverse vaccination (RV).
With respect to SARS-CoV-2, commensal microbial communities of the intestinal-lung axis could potentially induce innate cell-mediated immunity through an interaction with the mucosal epithelium. This coexistence could help achieve homeostasis and improve immune tolerance. Therefore, next-generation 2019 coronavirus disease vaccines (COVID-19) using specially designed bacterial mucosal vaccine vectors could manipulate and sequester commensal bacteria to elicit specific immune responses.
The study
In the present study, the researchers specifically sought and described research that discussed vectors of bacterial vaccines derived from the intestinal-lung axis and that are being tested as mucosal vaccines. In addition, they focused on three subdivisions of mucosal-associated lymphoid tissue (MALT), namely intestinal-associated lymphoid tissue (GALT), bronchial-associated lymphoid tissue (BALT), and associated lymphoid tissue. in the nasopharynx (NALT) and its interaction with the microbiome in the intestine-lung axis.
Dendritic cells (DC) in the gut are CD103 + and respond to T and B cells by a retinoic acid receptor-dependent mechanism. Immature DCs encompass pathogenic bacteria in the light and initiate the accumulation of new DCs to increase the rate of swallowing. In addition, these DCs induce auxiliary T cells, i.e., Th1 and Th17 cells, which favor a proinflammatory microenvironment.
To suppress this inflammatory state or inflammation of the mucosa, immature DCs are converted to tolerogenic DCs (tolDC) that facilitate the formation of regulatory helper T cells (Treg). Recurrent exposure of the same antigen to DCs induces a state of immune tolerance. Gamma delta T cells (γδ T cells) also play a crucial role in the mucous tissues of the lung and intestine.
In addition, DCs activate B cells independently or dependent on T cells. Similarly, secreted immunoglobulin A (SIgA) is a critical actor in GALT and promotes immune exclusion. For example, breastfeeding passes SIgA from a nursing mother to her baby and prevents gastrointestinal and respiratory infections. In addition, the IgG isotype binds to the bacterium and destroys it by lysis and activation of the complement system.
Tissue injury due to pathogens releases hazard-associated molecular patterns (DAMP), such as thermal shock proteins (HSPs), fibrinogen, and so on. However, only pathogen-associated molecular patterns (PAMPs) elicit an immune response, especially associated with viability (vita) -PAMPs, and are therefore promising candidate targets for developing new bacterial-based mucosal vaccines.
The authors found research citing various vita-PAMP, such as bacterial pyrophosphates, quorum detection molecules, cyclic diguanylate, etc., as vita-PAMP. In a study by Yang and co-workers, they observed that filamentous bacteria (SBF) induce Th17 production by their antigen, but produced Th1 when Listeria monocytogenes expressed the same antigen.
Studies have found that the lung is defended by highly specialized immune cells, such as alveolar macrophages and DC, a mucus barrier, type I and II hair epithelial cells, goblet cells, and so on. From a load of dead bacteria and other pathogens reaching the lung, the mucociliary elimination system (MCC) and macrophages induce an anti-inflammatory state in the lungs. Therefore, whenever the average load of any colonizing species naturally present in the upper respiratory tract increases, it elicits a pulmonary response; this could help the development of mucosal vaccines for respiratory infections.
The intestinal-lung axis could be a good site for mucosal vaccine vectors. The use of streptococcal species is not yet well studied. Marchisio and colleagues used Streptococcus salivarius as a prophylactic species and found that its recolonization correlated with a decrease in otopathogens and events of acute otitis media (AOM). In another study, Shekhar and co-workers showed that genetically modified strains of Streptococcus mitis produced a more specific response than their wild counterparts in the fight against pneumococcal lung infection in a mouse model.
Similarly, in a study by Wang et al., Genetically modified recombinant strains of Salmonella and Lactobacillus, especially L. plantarum that expressed the receptor-binding domain (RBD) of the SARS-CoV-2 S protein, caused mucosal IgA in the airways and intestines. deal. Jia and colleagues used a live attenuated holarctic vector of the subspecies Francisella tularensis to express SARS-CoV-2 S proteins, envelope, membrane, and nucleocapsid.
Conclusions
Future studies should focus on identifying dominant microbial species in several different niches (e.g., upper respiratory tract) for information on host-bacterial and interbacterial association networks. Knowledge of resident microbes, including their pathogenicity, scope of colonization, growth rate, etc., is necessary for host protection and immune homeostasis and vector-based vaccine design. bacterial mucosa with longer and stronger immunization profiles. Most importantly, studies should identify resident commensal species that release by-products and probiotics with a protective function. They represent an important potential to activate the immune system by maximizing the effect of mucosal vaccines.
Because the mechanism of action and limitations of current COVID-19 vaccines are unclear, the scientific community must continuously observe, prepare, and develop prophylactic, diagnostic, and therapeutic anti-SARS-CoV-2 tools. In addition, it would require new approaches to strengthen systemic immune defenses and natural mucous membranes.