Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world and became a pandemic that named coronavirus disease-2019 (COVID-19). At present, several intramuscular vaccines have been successfully developed and mass vaccination has progressed in many countries. The aim of the study is to develop and examine an oral vaccine against COVID-19 with recombinant Lactococcus lactis IL1403, a strain of lactic acid bacteria, expressing SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) S1 subunit as an immunizing antigen. PBS or cell extracts from recombinant L. lactis were orally administered into mice (control VS treatment), and formation of antigen-specific antibodies and changes in the gut microbiome were analyzed. Intracellular antigen was detected, but its secretion was not successful. After immunization, antigen-specific serum IgG and fecal IgA levels were 1.5-fold (P = 0.002) and 1.4-fold (P = 0.016) higher in the immunized mice (treatment) than control, respectively. Gut microbiome profiles were clearly separated between the two groups when analyzed for beta diversity with overall similarity. At the genus level, while Coprococcus (P = 0.036) and unclassified genus of Ruminococcaceae (P = 0.037) in treatment were more abundant than control, rc4-4 (P = 0.013) and Stenotrophomonas (P = 0.021) were less abundant. Our results indicate that cell extract containing SARS-CoV-2 antigen can induce mice to produce antigen-specific antibodies without overall changes in the gut microbiome. This strategy may be useful for the development of other oral viral vaccines.
【초록키워드】 COVID-19, Treatment, coronavirus disease, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, Vaccine, coronavirus, vaccination, pandemic, Vaccines, gut microbiome, severe acute respiratory syndrome Coronavirus, immunization, Oral vaccine, Antigen, coronavirus disease-2019, Spread, Protein, Viral, mice, RBD, Microbiome, Beta, Bacteria, SARS-CoV-2 antigen, respiratory, intramuscular, specific antibodies, SARS-CoV-2 spike, S1 subunit, strain, similarity, fecal, Gut, mass vaccination, acute respiratory syndrome, lactic acid, two groups, acute respiratory syndrome coronavirus, profile, secretion, domain, serum IgG, present, immunized mice, Intracellular, antigen-specific antibody, Administered, Cell, analyzed, develop, less, changes in, PBS, induce, two group, expressing, separated, IgA level, Lactococcus, progressed, 【제목키워드】 SARS-CoV-2, spike, oral, recombinant, Extract, Lactococcus,