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
Open accessAbstract
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.
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References 36 · Cited by 19
Research works printed but not linked: 1
- [16]Abeysundara, A. T., Aponso, M. & De Silva, G. A review on edible vaccines: A novel approach to oral immunization as a replacement of conventional vaccines.
- Authors
- Keikha, R., Hashemi-Shahri, S. M., & Jebali, A.
- Affiliations
- Zahedan University of Medical Sciences (IR)
- Islamic Azad University, Tehran (IR)
- Corresponding author
- Jebali, Ali
- ORCID
- Jebali, Ali
- Venue
- Scientific Reports
- Published
- 2021-10-29
- Volume
- 11
- Issue
- 1
- Pages
- 21308-21308
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC8556360
- OpenAlex
- W3210210298
- Cited by
- 19
- References
- 36
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 7 · 2022: 4
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Universidad de Navarra
- Zahedan University of Medical Sciences
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- oral vaccine, self-amplifying RNA, lipid nanoparticles, Lactobacillus plantarum, SARS-CoV-2, COVID-19 pandemic, S protein, neutralizing antibodies, IgA, IgG2a/IgG1 ratio, Th1 response, Alpha variant, Delta variant, small intestine
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Administration, Oral, Adult, Animals, Antibodies, Viral, Female, Humans, Immunoglobulin A, Immunoglobulin G, Intestine, Small, Lipids, Male, Mice, Inbred BALB C, Middle Aged, Neutralization Tests, RNA, Messenger, Tissue Distribution, Transfection, Vaccination, Vaccines, Synthetic, Models, Animal, Lactiplantibacillus plantarum, Mice, Nanoparticles, Antibodies, Neutralizing, HEK293 Cells, Spike Glycoprotein, Coronavirus
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