Targeted delivery of immunogen to primate m cells with tetragalloyl lysine dendrimer.
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.
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Shogo
S
Misumi
Mitsuaki
M
Masuyama
Nobutoki
N
Takamune
Daisuke
D
Nakayama
Ryotarou
R
Mitsumata
Hirokazu
H
Matsumoto
Norimitsu
N
Urata
Yoshihiro
Y
Takahashi
Atsunobu
A
Muneoka
Takayuki
T
Sukamoto
Koichiro
K
Fukuzaki
Shozo
S
Shoji
D000818:Animals; D000941:Antigens / Q000276:immunology; D018938:Caco-2 Cells; D050091:Dendrimers; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D018928:Immunity, Mucosal; D008239:Lysine / Q000008:administration & dosage* / Q000276:immunology; D008253:Macaca mulatta; D046529:Microscopy, Electron, Transmission; D010581:Peyer's Patches / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019713:Receptors, CCR5 / Q000276:immunology; D015302:Simian Immunodeficiency Virus; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000941:Antigens; D050091:Dendrimers; D019713:Receptors, CCR5; D014612:Vaccines; D008239:Lysine