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After invitro evaluation of the oral vaccines on HEK293T\/17 cells, we found that saRNA LNPs, saRNA transfected <jats:italic>Lactobacillus plantarum<\/jats:italic> LNPs, and saRNA transfected <jats:italic>Lactobacillus plantarum<\/jats:italic> 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 <jats:italic>Lactobacillus plantarum<\/jats:italic> LNPs, and saRNA transfected <jats:italic>Lactobacillus plantarum<\/jats:italic> at weeks 1 and 3. Importantly, a high titer of IgG and IgA was observed by all of them, sharply in week 6 (P\u2009&lt;\u20090.05). 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.<\/jats:p>","DOI":"10.1038\/s41598-021-00830-5","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T10:02:46Z","timestamp":1635501766000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The evaluation of novel oral vaccines based on self-amplifying RNA lipid nanparticles (saRNA LNPs), saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum to neutralize SARS-CoV-2 variants alpha and delta"],"prefix":"10.1038","volume":"11","author":[{"given":"Reza","family":"Keikha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Mohammad","family":"Hashemi-Shahri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Jebali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"830_CR1","first-page":"3435","volume":"11","author":"J Zhao","year":"2020","unstructured":"Zhao, J. et al. 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