| RRC ID |
87193
|
| Author |
Kawashima S, Takahashi K, Yanagisawa D, Irikura C, Kondo H, Inoue N, Koizumi J, Koshizuka T.
|
| Title |
Immunogenicity and plasmid delivery pathways of non-invasive Lactococcus lactis-vectored mucosal DNA vaccination.
|
| Journal |
Infect Immun
|
| Abstract |
Mucosal DNA vaccination using a non-invasive Lactococcus lactis (LL) vector has been investigated. However, its immunogenicity and plasmid transfer mechanisms remain largely unknown. In this study, we investigated the intranasal delivery of LL carrying a mammalian enhanced green fluorescent protein (EGFP)-expressing plasmid and the cellular pathways underlying DNA transfer. Intranasally administered LL was primarily localized on the nasal epithelial surfaces, and a smaller fraction penetrated the subepithelial tissues. Intranasal administration of LL-carrying pLEC-EGFP plasmid induces antigen-specific serum IgG and mucosal IgA responses. In vitro co-culture analyses demonstrated that plasmid delivery and expression occurred in phagocytic cell lines but not in epithelial cell lines. This transfer was inhibited by compounds specific for phagocytosis, consistent with the observed time course of DNA transfer and localization of LL within Lamp-1+ phagolysosomes. In contrast, compounds for bactericidal mechanisms, including lysosomal acidification, reactive oxygen species, and reactive nitrogen species, did not affect DNA transfer. As our findings suggest that phagocytosis is the primary pathway for plasmid delivery by non-invasive LL vectors in cell culture assays, further studies to confirm these findings in animal models are warranted to develop new strategies for improved LL-based mucosal DNA vaccines.
|
| Volume |
94(1)
|
| Pages |
e0046025
|
| Published |
2026-1-13
|
| DOI |
10.1128/iai.00460-25
|
| PMID |
41312987
|
| PMC |
PMC12798020
|
| MeSH |
Administration, Intranasal
Animals
Cell Line
Female
Genetic Vectors*
Green Fluorescent Proteins / genetics
Humans
Immunity, Mucosal
Immunoglobulin A
Immunoglobulin G / blood
Lactococcus lactis* / genetics
Lactococcus lactis* / immunology
Mice
Mice, Inbred BALB C
Phagocytosis
Plasmids* / genetics
Plasmids* / immunology
Vaccination / methods
Vaccines, DNA* / administration & dosage
Vaccines, DNA* / genetics
Vaccines, DNA* / immunology
|
| Resource |
| Human and Animal Cells |
THP-1 |
