Intranasal administration of Schistosoma japonicum paramyosin induced robust long-lasting systemic and local antibody as well as delayed-type hypersensitivity responses, but failed to confer protection in a mouse infection model.
To investigate intranasal (i.n.) immunization efficacy of Schistosoma japonicum 97-kDa myofibrillar protein paramyosin (PM), a vaccine candidate for Asian schistosomiasis, BALB/c mice were i.n. immunized with Escherichia coli-expressed recombinant PM (rPM). I.n. immunization using rPM mixed with cholera toxin (CT) was more potent than subcutaneous (s.c.) immunization with rPM emulsified in incomplete Freund's adjuvant for induction of serum (IgG, IgE, and IgA) and mucosal (IgA in nose, lung, and intestine) antibody and delayed-type hypersensitivity (DTH) responses. The second i.n. immunization was sufficient to induce maximal serum IgG and DTH responses, which were almost completely maintained for more than 6 months. Next, to evaluate protective efficacy of the rPM against S. japonicum infection, immunized mice were infected with S. japonicum cercariae at 2 weeks after the second immunization. At 7 weeks after infection, we observed no reduction in worm burden or fecundity in both i.n. and s.c. immunized groups. Results showed that i.n. immunization with rPM/CT failed to provide protection against parasite infection, albeit the antigen was a very potent mucosal immunogen. These results may emphasize the need to innovate new mucosal adjuvants or delivery molecules to overcome such hurdles in the construction of a mucosal antiparasite vaccine platform.
Kohama
Hideyasu
H
Molecular Microbiology Group, Department of Tropical Infectious Diseases, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Okinawa, Japan.
Harakuni
Tetsuya
T
Kikuchi
Mihoko
M
Nara
Takeshi
T
Takemura
Yasunori
Y
Miyata
Takeshi
T
Sato
Yoshiya
Y
Hirayama
Kenji
K
Arakawa
Takeshi
T
D000281:Administration, Intranasal; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D002772:Cholera Toxin; D004195:Disease Models, Animal; D004926:Escherichia coli; D005260:Female; D005620:Freund's Adjuvant; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000517:prevention & control; D014335:Tropomyosin / Q000008:administration & dosage / Q000276:immunology*
D000909:Antibodies, Helminth; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014335:Tropomyosin; D007371:Interferon-gamma; D005620:Freund's Adjuvant; D002772:Cholera Toxin