Targeted Delivery of Immunogen to Primate M Cells with Tetragalloyl Lysine Dendrimer
Open accessAbstract
Effective uptake of Ags by specialized M cells of gut-associated lymphoid tissues is an important step in inducing efficient immune responses after oral vaccination. Although stable nontoxic small molecule mimetics of lectins, such as synthetic multivalent polygalloyl derivatives, may have potential in murine M cell targeting, it remains unclear whether synthetic multivalent polygalloyl derivatives effectively target nonhuman and human M cells. In this study, we evaluated the ability of a tetragalloyl derivative, the tetragalloyl-d-lysine dendrimer (TGDK), to target M cells in both in vivo nonhuman primate and in vitro human M-like cell culture models. TGDK was efficiently transported from the lumen of the intestinal tract into rhesus Peyer’s patches by M cells and then accumulated in germinal centers. Oral administration of rhesus CCR5-derived cyclopeptide conjugated with TGDK in rhesus macaque resulted in a statistically significant increase in stool IgA response against rhesus CCR5-derived cyclopeptide and induced a neutralizing activity against SIV infection. Furthermore, TGDK was specifically bound to human M-like cells and efficiently transcytosed from the apical side to the basolateral side in the M-like cell model. Thus, the TGDK-mediated vaccine delivery system represents a potential approach for enabling M cell-targeted mucosal vaccines in primates.
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Lack of data on specific receptors on human M cells may make development of M-cell-specific targeting strategies more difficult than expected.
“As data on the expression of specific receptors on human M cells is lacking, the development of M-cell-specific targeting strategies, such as the coating of particles with lectins or lectin mimetics [117,119], might be more difficult than expected.”
From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [119]
Oral immunization with TGDK-conjugated multi antigens containing BSA and rhesus CCR5-derived cyclopeptide elicited mucosal rcDDR5-specific IgA with neutralizing activity.
“oral immunization with TGDK-conjugated multi antigens containing bovine serum albumin and a rhesus CCR5-derived cyclopeptide, which has recently been discussed as an attractive target for mucosal HIV-1 vaccines, elicited mucosal rcDDR5-specific IgA with neutralizing activity.”
From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [119]
After gavage of TGDK to rhesus macaques, the dendrimer was efficiently delivered to rhesus Peyer's patches' M cells in vivo.
“After gavage of TGDK to rhesus macaques, the dendrimer was efficiently delivered to rhesus Peyer’s patches’ M cells in vivo.”
From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [119]
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“Alternative approaches to target antigens to the a(1,2)fucose-containing carbohydrate moiety on M cells have also been explored, for example, by using the non-toxic, smallmolecular UEA-1 mimetic, tetragalloyl-D-lysine dendrimer.(98) The mAb NKM 16-2-4 specifically recognizes the a(1,2)fucose-containing carbohydrate mo…”
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Nanocarriers: a Versatile Approach for Mucosal Vaccine Delivery
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Role of nanoparticles in tackling COVID-19 pandemic: a bio-nanomedical approach
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Royal jelly enhances antigen‐specific mucosal IgA response
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Peyer’s Patch: Targeted Drug Delivery for Therapeutics Benefits
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- Authors
- Misumi, S., Masuyama, M., Takamune, N., Nakayama, D., Mitsumata, R., Matsumoto, H., Urata, N., Takahashi, Y., Muneoka, A., Sukamoto, T., Fukuzaki, K., & Shoji, S.
- Affiliations
- Kumamoto University (JP)
- Shin Nippon Biomedical Laboratories (Japan) (JP)
- Kumamoto Health Science University (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-05
- Volume
- 182
- Issue
- 10
- Pages
- 6061-6070
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1570333796
- Cited by
- 53
- References
- 55
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 1 · 2014: 3 · 2013: 7 · 2012: 5
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
- Keywords
- oral immunization, mucosal vaccines, Peyer's patches, germinal center, IgA antibody response, transcytosis, rhesus monkeys, nonhuman primate model, dendrimers
- MeSH terms
- Animals, Antigens, Female, Fluorescent Antibody Technique, Humans, Lysine, Macaca mulatta, Peyer's Patches, Vaccination, Vaccines, Simian Immunodeficiency Virus, Immunity, Mucosal, Caco-2 Cells, Receptors, CCR5, Microscopy, Electron, Transmission, Dendrimers
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