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.
Administration, Oral
Adult
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
COVID-19
/ blood
COVID-19 Vaccines
/ administration & dosage
Female
HEK293 Cells
Humans
Immunoglobulin A
/ blood
Immunoglobulin G
/ blood
Intestine, Small
/ metabolism
Lactobacillus plantarum
/ genetics
Lipids
/ chemistry
Male
Mice
Mice, Inbred BALB C
Middle Aged
Models, Animal
Nanoparticles
/ chemistry
Neutralization Tests
RNA, Messenger
/ genetics
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ immunology
Tissue Distribution
Transfection
/ methods
Vaccination
/ methods
Vaccines, Synthetic
/ administration & dosage
mRNA Vaccines
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 10 2021
29 10 2021
Historique:
received:
27
07
2021
accepted:
19
10
2021
entrez:
30
10
2021
pubmed:
31
10
2021
medline:
16
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34716391
doi: 10.1038/s41598-021-00830-5
pii: 10.1038/s41598-021-00830-5
pmc: PMC8556360
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
COVID-19 Vaccines
0
Immunoglobulin A
0
Immunoglobulin G
0
Lipids
0
RNA, Messenger
0
Spike Glycoprotein, Coronavirus
0
Vaccines, Synthetic
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21308Informations de copyright
© 2021. The Author(s).
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