ABSTRACT
Mucosal vaccines can effectively induce an immune response at the mucosal site and form the first line of defense against microbial invasion. The induced mucosal immunity includes the proliferation of effector T cells and the production of IgG and IgA antibodies, thereby effectively blocking microbial infection and transmission. However, after a long period of development, the transformation of mucosal vaccines into clinical use is still relatively slow. To date, fewer than ten mucosal vaccines have been approved. Only seven mucosal vaccines against coronavirus disease 2019 (COVID-19) are under investigation in clinical trials. A representative vaccine is the adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) developed by Chen and coworkers, which is currently in phase III clinical trials. The reason for the limited progress of mucosal vaccines may be the complicated mucosal barriers. Therefore, this review summarizes the characteristics of mucosal barriers and highlights strategies to overcome these barriers for effective mucosal vaccine delivery.
ABSTRACT
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. The symptoms of COVID-19 range from mild flu-like symptoms, including cough and fever, to life threatening complications. There are still quite a number of patients with COVID-19 showed enteric symptoms including nausea, vomiting, and diarrhea. The gastrointestinal tract may be one of the target organs of SARS-CoV-2. Angiotensin converting enzyme 2 (ACE2) is the main receptor of SARS-CoV-2 virus, which is significantly expressed in intestinal cells. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Intestinal flora imbalance and endotoxemia may accelerate the progression of COVID-19. Many herbs have demonstrated properties relevant to the treatment of COVID-19, by supporting organs and systems of the body affected by the virus. Herbs can restore the structure of the intestinal flora, which may further modulate the immune function after SARS-CoV-2 infection. Regulation of intestinal flora by herbal medicine may be helpful for the treatment and recovery of the disease. Understanding the role of herbs that regulate intestinal flora in fighting respiratory virus infections and maintaining intestinal flora balance can provide new ideas for preventing and treating COVID-19.
ABSTRACT
Mucus plays a pivotal role in protecting the respiratory tract against microbial infections. It acts as a primary contact site to entrap microbes and facilitates their removal from the respiratory tract via the coordinated beating of motile cilia. The major components of airway mucus are heavily O-glycosylated mucin glycoproteins, divided into gel-forming mucins and transmembrane mucins. The gel-forming mucins MUC5AC and MUC5B are the primary structural components of airway mucus, and they enable efficient clearance of pathogens by mucociliary clearance. MUC5B is constitutively expressed in the healthy airway, whereas MUC5AC is upregulated in response to inflammatory challenge. MUC1, MUC4, and MUC16 are the three major transmembrane mucins of the respiratory tracts which prevent microbial invasion, can act as releasable decoy receptors, and activate intracellular signal transduction pathways. Pathogens have evolved virulence factors such as adhesins that facilitate interaction with specific mucins and mucin glycans, for example, terminal sialic acids. Mucin expression and glycosylation are dependent on the inflammatory state of the respiratory tract and are directly regulated by proinflammatory cytokines and microbial ligands. Gender and age also impact mucin glycosylation and expression through the female sex hormone estradiol and age-related downregulation of mucin production. Here, we discuss what is currently known about the role of respiratory mucins and their glycans during bacterial and viral infections of the airways and their relevance for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the impact of microbe-mucin interaction in the respiratory tract could inspire the development of novel therapies to boost mucosal defense and combat respiratory infections.