Effective vaginal DNA delivery with high transfection efficiency is a good system for induction of higher local vaginal immune responses.
OBJECTIVE
To investigate the local vaginal and systemic immune responses of effective vaginal DNA delivery with high transfection efficiency, we determined the effects on Th1-dependent cytokine (interferon-gamma) production in spleen and inguinal lymph node cells and antibody responses of vaginal pDNA immunization with a cell-penetrating peptide, and compared our vaginal immunization with intradermal and intranasal immunizations.


METHODS
Mice were immunized by vaginal, nasal or dermal administration of pCMV-OVA with or without peptide carriers, and serum, vaginal fluids, spleen and inguinal cells were harvested. The serum immunoglobulin (Ig)G(2a) and vaginal IgA antibody responses were determined by sandwich enzyme-linked immunosorbent assay (ELISA). The interferon-gamma production from spleen cells or inguinal lymph node cells was determined by an ELISA kit.


RESULTS
The direct vaginal immunization strongly induced IgA in the vaginal fluids and interferon-gamma production in the local lymph node draining from the vagina. In addition, co-vaccination with the peptide carriers elevated these immune responses compared with vaccination with pCMV-OVA alone. Vaginal immunization with high transfection efficiency promoted vaginal IgA production to a significantly greater extent than intradermal or nasal immunization.


CONCLUSIONS
These results suggested that direct vaginal DNA vaccines under high transfection conditions induced higher local vaginal antibody than that by intranasal or intradermal administration, and peptide carriers effectively elevated mucosal immune responses. Therefore, this vaginal DNA vaccination method may be expected to be useful in the prevention and treatment methods for vaginal infectious diseases such as HIV infection.
Kanazawa
Takanori
T
Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan. kanazawa@toyaku.ac.jp
Takashima
Yuuki
Y
Shibata
Yasunori
Y
Tsuchiya
Miki
M
Tamura
Toshiaki
T
Okada
Hiroaki
H
D000282:Administration, Intravaginal; D000818:Animals; D005260:Female; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods*; D007070:Immunoglobulin A / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood; D007372:Interferons / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells; D014162:Transfection / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014621:Vagina / Q000276:immunology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D010047:Ovalbumin; D007372:Interferons