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Shin-ichi Tamura

Publications and source records attributed to Shin-ichi Tamura.

11 recordsLinked to original sources
PubMed2006

Protection against influenza virus infection by intranasal vaccine with surf clam microparticles (SMP) as an adjuvant.

A safe and effective adjuvant is necessary to enhance mucosal immune responses for the development of an inactivated intranasal influenza vaccine. The present study demonstrated the effectiveness of surf clam microparticles (SMP) derived from natural surf clams as an adjuvant for an intranasal influenza vaccine. The adjuvant effect of SMP was examined when co-administered intranasally with inactivated A/PR8 (H1N1) influenza virus hemagglutinin vaccine in BALB/c mice. Administration of the vaccine with SMP induced a high anti-PR8 haemagglutinin (HA)-specific immunoglobulin A (IgA) response in the nasal wash and immunoglobulin G (IgG) response in the serum, resulting in protection against both nasal-restricted infection and lethal lung infection by A/PR8 virus. In addition, administration of SMP with A/Yamagata (H1N1), A/Beijing (H1N1), or A/Guizhou (H3N2) vaccine conferred complete protection against A/PR8 virus challenge in the nasal infection model, suggesting that SMP adjuvanted vaccine can confer cross-protection against variant influenza viruses. The use of SMP is suggested as a new safe and effective mucosal adjuvant for nasal vaccination against influenza virus infection.

Adjuvants, Immunologic↗
PubMed2006

[Intranasal inactivated influenza vaccine].

Natural influenza virus infection is well known to be superior to parenteral inactivated vaccines, which induce serum IgG antibodies(Abs) alone, in inducing the broad-spectrum cross-protection against variant virus infection. Secretory IgA Abs, which provide cross-protection strongly against infection with variant viruses within the same subtype mainly in the upper respiratory tract, serum IgG Abs, which provide cross-protection weakly against infection with variant viruses mainly in the lower respiratory tract, and cytotoxic T lymphocytes, which provide cross-protection against infection with different subtype viruses and whose role is not always big in humans, are involved in the defence mechanisms induced by natural infection. The development of intranasal inactivated vaccine, capable of inducing both IgA and IgG Abs, is important to improve the efficacy of current inactivated vaccine.

Adjuvants, Immunologic↗
PubMed2005

Estimation of the neuraminidase content of influenza viruses and split-product vaccines by immunochromatography.

The neuraminidase (NA) of the influenza virus, as well as the hemagglutinin, is the most important protective components in the vaccine. However, the NA content of the vaccine remains to be standardized because of the labile nature of this glycoprotein during various chemical treatments and storage. In the present study, the NA content of the split-product (SP) vaccine (virus treated with ether then formalin) was estimated together with that of the virus by an immunochoromatography technique using monoclonal antibodies (mAbs) to viral NA for A/Panama/2007/99 (A/Pa) (H3N2), B/Shangdong/7/97 (B/S) or A/New Caledonia/20/99 (A/NC) (H1N1) viral strains. In the new method, the NA catalytic activity of each fraction from steps of NA purification was measured as an index of NA content. The NA level of A/Pa, B/S or A/NC viral particles was estimated at 6.9+/-0.9, 7.6+/-0.8 or 8.5+/-1.7% of total viral protein (not significant difference between viral strains). The NA level of the corresponding A/Pa, B/S or A/NC vaccines was estimated at 9.6+/-1.5, 12.7+/-0.4 or 12.2+/-1.2% of the total vaccine protein (a significant difference between each strain of virus and its vaccine). These results suggest that the NA content in the N1, N2 or B type NA virus ranges from 5 to 11% of the total viral protein, and that the NA level in each split-product vaccine is 1.4- to 1.6-fold higher than that in the corresponding viral particles. They also suggest that the NA content can be estimated by the immunochoromatography technique using anti-viral NA mAbs.

Animals↗
PubMed2005

Mechanisms of broad cross-protection provided by influenza virus infection and their application to vaccines.

Mice recovered from influenza A virus infection have been shown to be cross-protected against challenge infection with either drift viruses within a subtype (subtype-specific immunity) or different subtype viruses (heterosubtypic immunity). The mechanisms of broad-spectrum of cross-protection could be explained as follows. (i) Pre-existing S-IgA and IgG antibodies (Abs) induced by infection are involved in the elimination of challenge viruses by forming virus-Ig complexes shortly after re-infection. Due to their polymeric nature, the S-IgA Abs, existing more abundant on the mucosa than are IgG Abs, are strongly cross-reactive with challenge viruses, whereas the IgG Abs are weakly cross-reactive with challenge viruses, due to their monomeric nature. The specificity of Abs is directed mainly at hemagglutinin and neuraminidase. (ii) CD8+ memory T cells induced by infection are involved in the elimination of challenge viruses by the accelerated killing of host cells infected with different subtype viruses from day 3 onwards after re-infection. The specificity of memory T cells is directed against viral internal proteins. (iii) The accelerated IgA and IgG Ab responses, produced by B memory cells after a challenge, are also involved in cross-protection from day 4 onwards after re-infection. (iv) In the epithelial cells of infected mice, dimeric IgA that is trafficked through the epithelial cells can contribute to the prevention of viral assembly by binding to newly synthesized viral proteins. Natural infection is well known to be superior to parenteral inactivated vaccines in inducing the broad-spectrum cross-protection. To improve the efficacy of current inactivated vaccines, many trials have been conducted to mimic natural infection, including intranasal or epidermal administration of inactivated vaccine with or without an adjuvant; such studies are still ongoing. In the near future, some of these trials may provide new, safer and more effective broad-spectrum vaccines than those currently available.

Administration, Cutaneous↗
PubMed2004

Defense mechanisms against influenza virus infection in the respiratory tract mucosa.

The respiratory tract mucosa is not only the site of infection for influenza viruses but also the site of defense against virus infection. Viruses are initially detected and destroyed non-specifically by innate immune mechanisms, but if the viruses escape the early defense mechanisms, they are detected and eliminated specifically by adaptive immune mechanisms. The major adaptive immune mechanisms are as follows. (i) Specific secretory-IgA (S-IgA) antibodies (Abs) and CTLs (CD8+ cytotoxic T lymphocytes) are involved in the recovery from influenza following viral infection of naive mice. (ii) Preexisting specific S-IgA and IgG Abs in the immunized animals are involved in viral elimination by forming virus-Ig complexes shortly after re-infection. By their polymeric nature, the S-IgA Abs, which are carried to the mucus by transepithelial transport used for dimeric IgA (dIgA) Abs, provide not only protection against homologous virus infection but also cross-protection against drift virus infection. The IgG Abs, which transude from the serum to the mucus by diffusion, provide protection against homologous virus infection. They are largely distributed on the alveolar epithelia to prevent influenza pneumonia. (iii) In the absence of Abs in the pre-immunized animals, the production of specific IgA and IgG Abs by B memory cells is accelerated after re-infection, and these antibodies play a role in viral elimination from day 3 onwards after re-infection. (iv) In epithelial cells of infected animals, specific dIgA Abs being trafficked through the epithelial cells may be involved in the prevention of viral assembly by binding to newly synthesized viral proteins. (v) In the pre-immunized animals, CTL production by memory T cells is also accelerated and these cells appear to participate in the killing of the host cells infected with different subtype viruses (within the same type) from day 3 onwards after re-infection. (vi) Similarly, memory Th1 cells that mediate an accelerated delayed-type hypersensitivity response are involved in blockade of virus replication by secreting IFN-gamma in mice challenged with different subtype viruses. These defense mechanisms suggest that the development of a mucosal vaccine, capable of inducing S-IgA Abs, which provide cross-protection against variant viruses within the same subtype, serum IgG Abs to prevent lethal influenza pneumonia and CTLs, which provide broad cross-protection against different subtype viruses, is strategically important to control influenza.

Animals↗
PubMed2003

Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin.

For the induction of mucosal immune responses by intranasal vaccination, cholera toxin B subunits (CTB) and Escherichia coli heat-labile toxin (LT) are often administered as mucosal adjuvants in order to enhance immune responses to mucosally co-administered bystander antigens. However, these toxin also are the causative agents of diarrhea. There is a demand for the establishment of an effective and safer adjuvant or vaccine that elicits mucosal immunity, but does not require the use of CTB or LT adjuvants. In order to induce protective mucosal immune responses in the nasal area against influenza virus infection, we have examined the recombinant protein composed of the complement component, C3d, which is fused to the secreted form of hemagglutinin (sHA-mC3d3) in the influenza-BALB/c mouse model. The fusion protein sHA-mC3d3, the secretory form of hemagglutinin, and the transmembrane form of HA (tmHA) from the influenza virus were intranasally administered to the mice with or without CTB containing a trace amount of holotoxin (CTB*) as an adjuvant. After intranasal administration of these proteins with CTB*, all mice produced nasal IgA and serum IgG antibodies (Abs) against the viral HA. In addition, viral infection was completely inhibited in these mice. In contrast, in the absence of the adjuvant, only sHA-mC3d3-induced locally secreted IgA and serum IgG Abs and provided complete protection against the influenza virus challenge. Thus, C3d fused to the influenza HA antigen is an effective and safe tool for mucosal vaccination.

Adjuvants, Immunologic↗
PubMed2003

Roles of anti-hemagglutinin IgA and IgG antibodies in different sites of the respiratory tract of vaccinated mice in preventing lethal influenza pneumonia.

The roles of IgA and IgG antibodies (Abs) against hemagglutinin (HA) in the prevention of lethal influenza pneumonia in vaccinated mice were examined in terms of distribution and concentration of the Abs in the mucus or the serous fluid in different sites of the respiratory tract (RT), mucosa of the nose, trachea, bronchi and bronchioli and the alveolar epithelia of pulmonary acinus. First, the surface areas of the tracheal, bronchial and bronchiolar mucosa and alveolar epithelia were measured to be 20, 260 and 217, 433 mm(2), respectively, using serial tissue sections of the trachea and lungs. Then, the volumes of the tracheal mucus, the bronchial and bronchiolar mucus and the serous fluid of alveolar epithelia were estimated to be 0.2, 2.6 and 21.7 mm(3), respectively, by calculating each from the surface area and an assumed thickness of the mucus layer (0.01 mm) or that of the serous fluid (0.0001 mm). Next, anti-HA IgA and IgG Ab responses in the nasal wash, the trachea-lung wash and the trachea wash were measured in BALB/c mice immunized intranasally with an adjuvant-combined A/PR/8/34 (H1N1) virus vaccine and challenged with a lethal dose of the virus. Then the values of Ab responses were converted to the mucus and serous fluid Ab concentration based on two premises that the serum Abs diffuse at a constant rate to the surface of the tracheal, bronchial and bronchiolar mucosa, and that the active transepithelial transport of IgA Abs does not work in the alveolar epithelia. Results showed that 21.4 microg/ml IgA Abs and 3.6 microg/ml IgG Abs in the tracheal mucus (19.1 and 0.3% of the trachea-lung wash IgA and IgG Ab amounts, respectively), 5.9 microg/ml IgA Abs and 3.6 microg/ml IgG Abs in the bronchial and bronchiolar mucus (66.0 and 3.4% of the trachea-lung wash IgA and IgG Ab amounts, respectively) and about 0.1 microg/ml IgA Abs and 12.3 microg/ml IgG Abs in the serous fluid of alveolar epithelia (14.9 and 96.3% of the trachea-lung wash IgA and IgG Ab amounts, respectively) were present in the vaccinated mice, at which concentrations influenza pneumonia was prevented. Thus, 96.3% of anti-HA IgG Abs in the trachea-lung wash work on the alveolar epithelia, whose surface area is about 800 times larger than that of tracheal, bronchial and bronchiolar mucosa and seem to play a more important role than the mucosal IgA Abs in the prevention of lethal influenza pneumonia.

Animals↗
PubMed2003

[Present situation of influenza vaccine development].

Influenza is a highly contagious acute respiratory disease, caused by influenza viruses infecting the host at the respiratory mucosa and repeated annually by appearance of variant viruses with altered surface antigens. To control influenza, a protective immunity must be provided in advance by administration with an inactivated or attenuated virus vaccine. Current inactivated vaccine, licensed for parenteral administration, can induce systemic IgG antibodies, but not highly cross-reactive mucosal IgA and heterosubtypic cytotoxic T lymdhocytes(CTL), to results in lowered protective efficacy against variant virus infection. Current attenuated virus vaccine, licensed for intranasal administration, can induce IgA and CTL, as well as IgG, with coryza, sore throat and febrile reactions and with forbidden use to high-risk patients. To improve shortcomings of the current inactivated or attenuated vaccine, many trials, including the development of DNA vaccine, are still going on.

Antibodies, Viral↗
PubMed2002

Characterization of protective immune responses induced by nasal influenza vaccine containing mutant cholera toxin as a safe adjuvant (CT112K).

Immune responses induced by a nasal influenza vaccine with a mutant cholera toxin (CT112K), known to be a safe adjuvant, were characterized in BALB/c mice to confirm the most suitable regimen of this vaccine for humans. Mice received a primary intranasal administration of the adjuvant (0.1 micro g)-combined PR8 vaccine (0.1 micro g) and a secondary administration of the PR8 vaccine alone (0.1 micro g) 4 weeks later. Two weeks after the secondary immunization, the mice were infected with a nonlethal or a lethal dose of PR8 viruses. Nasal and lung wash virus titers 1 or 3 days after infection indicated that complete protection could be provided by secondary immune responses, which had an immediate effect of preventing infection 2 weeks after the secondary immunization. In this two-dose regimen, high levels of secondary IgA, IgG and IgM antibody-forming cell (AFC) responses were induced in the nasal-associated lymphoid tissue and the spleen. In parallel with the AFC responses, high levels of nasal wash anti-PR8 HA IgA, and lung and serum IgG antibody (Ab) responses were induced 2 weeks after the secondary immunization. The two-dose regimen also induced accelerated delayed-type hypersensitivity responses, which exhibited almost the same peak height as that in the case of the primary response. In addition, the two-dose regimen induced a low memory cell activity of cytotoxic T lymphocytes, detected by in vitro culture of spleen cells. Thus, the immediate effect of preventing infection was mainly provided by the secondary Ab responses. Moreover, the levels of nasal wash IgA Abs correlated well with cross-protection against infection with variant viruses in the upper respiratory tract (RT). These results suggest that the major protective factors among Ab and T cell-mediated immune responses, which are induced by the two-dose regimen using CT112K-combined vaccines, are the cross-reactive IgA Abs in the upper RT and the less cross-reactive IgG Abs in the lower RT, and that the two-dose regimen is a suitable vaccination condition for humans.

Adjuvants, Immunologic↗
PubMed2002

Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines.

The role of secretory IgA in conferring cross-protective immunity was examined in polymeric (p)IgR knockout (KO) mice immunized intranasally with different inactivated vaccines prepared from A/PR/8/34 (H1N1), A/Yamagata/120/86 (H1N1), A/Beijing/262/95 (H1N1), and B/Ibaraki/2/85 viruses and infected with the A/PR/8/34 virus in the upper respiratory tract (RT)-restricting volume. In wild-type mice, immunization with A/PR/8/34 or its variant (A/Yamagata/120/86 and A/Beijing/262/95) vaccines conferred complete protection or partial cross-protection against infection, while the B-type virus vaccine failed to provide protection. The protection or cross-protection was accompanied by an increase in the nasal A/PR/8/34 hemagglutinin-reactive IgA concentration, which was estimated to be >30 times the serum IgA concentration and much higher than the nasal IgG concentration. In contrast, the blockade of transepithelial transport of dimeric IgA in pIgR-KO mice reduced the degree of protection or cross-protection, in parallel with the marked increase in serum IgA concentration and the decrease in nasal IgA concentration (about 20 and 0.3 times those in wild-type mice, respectively). The degree of the reduction of protection or cross-protection was moderately reversed by the low but non-negligible level of nasal IgA, transudates from the accumulated serum IgA. These results, together with the absence of the IgA-dependent cross-protection in the lower RT and the unaltered level of nasal or serum IgG in wild-type and pIgR-KO mice, confirm that the actively secreted IgA plays an important role in cross-protection against variant virus infection in the upper RT, which cannot be substituted by serum IgG.

Adjuvants, Immunologic↗