Takashi Kimoto

Publications (3)11.69 Total impact

• Article: Induction and maintenance of anti-influenza antigen-specific nasal secretory IgA levels and serum IgG levels after influenza infection in adults.

  Chisa Fujimoto, Noriaki Takeda, Atsushi Matsunaga, Ayako Sawada, Takeshi Tanaka, Takashi Kimoto, Wakako Shinahara, Takako Sawabuchi, Miyoko Yamaguchi, Masaki Hayama, Hiroaki Yanagawa, Mihiro Yano, Hiroshi Kido
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  ABSTRACT: Please cite this paper as: Fujimoto et al. (2012) Induction and maintenance of anti-influenza antigen-specific nasal secretory IgA levels and serum IgG levels after influenza infection in adults. Influenza and Other Respiratory Viruses 6(6), 396-403. Objectives  To determine the induction and changes in anti-influenza virus secretory IgA (s-IgA) levels in nasal washes and serum IgG levels in patients with influenza. Methods  The study recruited 16 patients with influenza aged 35·6 ± 9·6 years in 2007/2008 and 2008/2009 seasons. Nasal washes and serum were obtained throughout the first year. Anti-viral s-IgA levels and neutralization activities in nasal washes, and serum anti-viral IgG levels and hemagglutination inhibition (HI) titers were measured. Results  Anti-viral(H1N1) s-IgA to total IgA ratio and neutralizing antibody titer were low in nasal washes of all patients, whereas serum levels of anti-viral IgG and HI titers varied widely at day 1·4 ± 1·0 postinfection. Both nasal s-IgA and serum IgG levels later increased significantly, reaching peak levels at day 9·6 ± 3·3 postinfection. The induced nasal s-IgA then returned toward the initial levels within 300 days, although the levels at day 143 ± 70 were 3·03-fold of the initial. Individual serum IgG levels also returned toward the initial levels within 300 days, although the mean levels remained high probably because of re-infection in a subgroup of patients. Although influenza A (H3N2) was a minor epidemic subtype in both flu seasons, a significant rise in nasal anti-viral (H3N2) s-IgA levels and a slightly increase in serum IgG levels were noted. Conclusion  Low levels of nasal anti-viral s-IgA and neutralizing antibody were noted compared with a wide range of serum anti-viral IgG and HI titers at the onset of infection. Elevated s-IgA and IgG returned toward the initial levels within 300 days of infection with minor exceptions.
  Influenza and Other Respiratory Viruses 01/2012; 6(6):396-403. · 4.16 Impact Factor
• Article: Surfactant protein C is an essential constituent for mucosal adjuvanticity of Surfacten, acting as an antigen delivery vehicle and inducing both local and systemic immunity.

  Dai Mizuno, Takashi Kimoto, Tsunetomo Takei, Akiho Fukuta, Wakako Shinahara, Etsuhisa Takahashi, Mihiro Yano, Hiroshi Kido
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  ABSTRACT: We have reported that Surfacten(®) (St), a bovine pulmonary surfactant free of antigenic c-type lectins, is a useful mucosal adjuvant for nasal vaccination. To prepare ample supplies a synthetic adjuvant that mimics St, we analyzed essential constituents of St for mucosal adjuvanticity. Intranasal inoculation of influenza virus hemagglutinin (HA) vaccine combined with St free of surfactant protein (SP)-C resulted in failure of HA vaccine delivery to dendritic cells and loss of local and systemic immune responses. Naïve bovine SP-C, synthetic human or bovine SP-C peptide reconstituted with three major St lipids restored delivery activity and local and systemic immune responses to levels similar to those of St and provided almost complete protection against lethal doses of influenza virus challenge in mice. The delivery of fluoresceinated HA vaccine to cultured dendritic cells was significantly enhanced by co-administration of St or synthetic adjuvant, and moderately stimulated the expression of MHC class II and CD86. In addition, both St and synthetic adjuvant markedly sustained HA vaccine and achieved a wide antigen distribution in murine nasal cavity. These results suggest that synthetic mucosal adjuvant reconstituted with SP-C peptide and major St lipids is useful for ample supply of the potent mucosal adjuvant as an antigen delivery vehicle for intranasal vaccination.
  Vaccine 06/2011; 29(33):5368-78. · 3.77 Impact Factor
• Article: Influenza vaccine with Surfacten, a modified pulmonary surfactant, induces systemic and mucosal immune responses without side effects in minipigs.

  Maki Nishino, Dai Mizuno, Takashi Kimoto, Wakako Shinahara, Akiho Fukuta, Tsunetomo Takei, Kaori Sumida, Seiichiro Kitamura, Hiroshi Shiota, Hiroshi Kido
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  ABSTRACT: Immune responses and side effects of intranasally administered flu vaccine with the commercial product Surfacten, a modified bovine pulmonary surfactant, were investigated in minipigs. The use of minipigs was based on the anatomical resemblance of nasal lymph nodes, the principal antigen uptake site of respiratory mucosal immunity, between pig and human. Intranasal instillation of HA vaccine adjuvanted with Surfacten elicited significantly higher serum hemagglutination inhibition titers than the antigen alone, with wide cross-neutralizing activities of secretory IgA in nasal washes. No significant induction of inflammatory cytokines or migration of inflammatory cells was observed at the site of immunization or serum after the first immunization. These data suggest the potential usefulness of Surfacten for mucosal vaccination.
  Vaccine 08/2009; 27(41):5620-7. · 3.77 Impact Factor