The aim of this study was to present and evaluate novel oral vaccines, based on self-amplifying RNA lipid nanparticles (saRNA LNPs), saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum , to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants alpha and delta. After invitro evaluation of the oral vaccines on HEK293T/17 cells, we found that saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum could express S-protein at both mRNA and protein levels. In the next step, BALB/c mice were orally vaccinated with saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum at weeks 1 and 3. Importantly, a high titer of IgG and IgA was observed by all of them, sharply in week 6 (P < 0.05). In all study groups, their ratio of IgG2a/IgG1 was upper 1, indicating Th1-biased responses. Wild-type viral neutralization assay showed that the secreted antibodies in vaccinated mice and recovered COVID-19 patients could neutralize SARS-COV-2 variants alpha and delta. After oral administration of oral vaccines, biodistribution assay was done. It was found that all of them had the same biodistribution pattern. The highest concentration of S-protein was seen in the small intestine, followed by the large intestine and liver.
【저자키워드】 immunology, Vaccines, RNA vaccines, 【초록키워드】 IgG, coronavirus, antibody, variant, severe acute respiratory syndrome Coronavirus, Oral vaccine, RNA, Viral, cells, mice, IgA, oral vaccines, mRNA, intestine, Alpha, viral neutralization, respiratory, liver, IgG1, biodistribution, administration, Recovered COVID-19 patients, S-protein, Concentration, followed by, oral administration, acute respiratory syndrome, large intestine, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, small intestine, IgG2a, study groups, Express, BALB/c mice, protein levels, saRNA, responses, lactobacillus, recovered COVID-19 patient, neutralize, highest, evaluate, was done, secreted, 【제목키워드】 SARS-CoV-2 variant, Oral vaccine, RNA, lactobacillus, neutralize,