Predominant cell-mediated immunity in the oral mucosa: gene gun-based vaccination against infectious diseases.
BACKGROUND
Direct immunization via epithelial surfaces has been considered for many vaccine approaches, including DNA vaccines. It remains to be determined, however, which body site is suitable for genetic vaccination.


OBJECTIVE
To characterize the effects of the oral mucosa-mediated genetic vaccination, we compared antigen-specific immune responses of the oral mucosal DNA vaccine to the flank skin vaccination against influenza virus and malaria parasite.


METHODS
DNA vaccines against the influenza A/WSN/33 (H1N1) hemagglutinin and the malaria Plasmodium berghei circumsporozoite protein were administered respectively three times at 3-week intervals into the oral mucosa, skin, or liver of hamsters. The effects of their vaccine were evaluated by antigen-specific antibody production and cell-mediated killing activity. Furthermore, the in vivo malaria challenge test was also performed after the vaccination.


RESULTS
Significant specific antibody production was not observed in each case, but interferon-gamma production and cell-mediated killing activity were strongly induced in splenic lymphocytes from hamsters with the oral vaccination. The in vivo malaria challenge after the oral mucosal vaccination significantly delayed the blood-appearance day of the parasites in comparison with other immunization sites (P<0.05).


CONCLUSIONS
These results suggest that gene immunization via the oral mucosa may induce cell-mediated immunity more efficiently than via the skin or liver, and that the oral mucosa may be one of the most suitable tissues for gene gun-based DNA vaccination against infectious diseases.
Center for Molecular Medicine, Division of Organ Replacement Research and Molecular Immunology, Jichi Medical School 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan.
Jun
J
Wang
Takashi
T
Murakami
Shigeto
S
Yoshida
Hiroyuki
H
Matsuoka
Akira
A
Ishii
Toshinori
T
Tanaka
Kiyotake
K
Tobita
Mamitaro
M
Ohtsuki
Hidemi
H
Nakagawa
Mikio
M
Kusama
Eiji
E
Kobayashi
D000818:Animals; D019470:Biolistics / Q000379:methods*; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007239:Infections / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics*; D007252:Influenza Vaccines; D017780:Malaria Vaccines; D008647:Mesocricetus; D010962:Plasmodium berghei / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA
D007252:Influenza Vaccines; D017780:Malaria Vaccines; D019444:Vaccines, DNA