Hacking Commensal Bacteria to Consolidate the Adaptive Mucosal Immune Response in the Gut–Lung Axis: Future Possibilities for SARS-CoV-2 Protection

Abstract

Infectious diseases caused by mucosal pathogens significantly increase mortality and morbidity. Thus, the possibility to target these pathogens at their primary entry points can consolidate protective immunity. Regarding SARS-CoV-2 infection, it has been observed that the upper respiratory mucosa is highly affected and that dysregulation of resident microbiota in the gut–lung axis plays a crucial role in determining symptom severity. Thus, understanding the possibility of eliciting various mucosal and adaptive immune responses allows us to effectively design bacterial mucosal vaccine vectors. Such design requires rationally selecting resident bacterial candidates as potential host carriers, evaluating effective carrier proteins for stimulating an immune response, and combining these two to improve antigenic display and immunogenicity. This review investigated mucosal vaccine vectors from 2015 to present, where a few have started to utilize Salmonella and lactic acid bacteria (LAB) to display SARS-CoV-2 Spike S proteins or fragments. Although current literature is still lacking for its studies beyond in vitro or in vivo efficiency, decades of research into these vectors show promising results. Here, we discuss the mucosal immune systems focusing on the gut–lung axis microbiome and offer new insight into the potential use of alpha streptococci in the upper respiratory tract as a vaccine carrier.

Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice

“…Lactobacilli, including Lacticaseibacillus rhamnosus, Lacticaseibacillus casei, Latilactobacillus sakei , and L. plantarum , are relatively enriched in the upper respiratory tract, specifically in the anterior nares and nasopharynx of healthy individuals [ 42 ]. The oral consumption of commercial probiotics can contribute to niche colonization in the upper respiratory tract because of their anatomical connection via the nasopharynx, making them well adapted for possible development as a commensal mucosal prophylactic vector [ 43 , 44 ]. In addition, L. plantarum strains are robust vaccine delivery systems and are well-characterized species, specifically in adhesion to mucosal surfaces and close interaction with host epithelial cells.…”

Unraveling the gut-Lung axis: Exploring complex mechanisms in disease interplay

“…This limitation is majorly due to consistent exposure of gut bacteria to other microbial species, human physiology, diet, medications, etc. Therefore, tailoring microbiota composition during disease, considering the influences of various factors especially antibiotics, adds crucial understanding and are essential to derive novel therapeutic approaches [ 101 ].…”

“…Recently CRISPR-Cas based gene editing technology on gut microbes propose a promising tool for microbiota manipulation [ 103 ]. Additionally, commensal bacterial species were proposed to be the mucosal vaccine vectors [ 104 , 105 ] and purified encapsulated microbiota of a “healthy donors” are already considered [ 106 ], though further validation for translation is required for these studies. Although the DNA content from fecal samples can determine the ecological and evolutionary changes mediated by different factors on microbes, the real time adaptation to evolving environmental changes at their gene expression level is not reflected in DNA [ 107 ] .…”

Immunological profile of diabetic foot ulcers: update review

“…In addition, bacteria typically create biofilms that thwart immune clearance and encourage the development of antimicrobial resistance; in one research, 78.2% of chronic wounds exhibited biofilm creation. To guide the development of innovative therapies and inform antimicrobial therapy, a deeper comprehension of the microbiology of DFIs is crucial [22,23].…”