Protective effect of nasal immunization of influenza virus hemagglutinin with recombinant cholera toxin B subunit as a mucosal adjuvant in miceIsaka, Masanori; Zhao, Yanqiu; Nobusawa, Eri; Nakajima, Setsuko; Nakajima, Katsuhisa; Yasuda, Yoko; Matsui, Hideyuki; Hasegawa, Tadao; Maeyama, Jun‐ichi; Morokuma, Kazunori; Ohkuma, Kunio; Tochikubo, Kunio
doi: 10.1111/j.1348-0421.2008.00010.xpmid: 18380802
To develop an efficient nasal influenza vaccine, influenza A and B virus HA with rCTB as a mucosal adjuvant were administered to mice intranasally. Serum anti‐HA IgG and IgA antibody responses for both HA vaccines were significantly increased in the presence of rCTB. Higher HI and neutralizing antibody titers and higher mucosal IgA antibody responses in the respiratory tract were detected when rCTB was added than without rCTB. When mice were immunized with HA vaccine with or without rCTB and challenged by intranasal administration of mouse‐adapted pathogenic influenza A virus, all mice immunized with HA plus rCTB survived for seven days without any inflammatory changes in the lungs, while not all the mice immunized with HA without rCTB survived, and all of them had lung consolidations. These results demonstrate that intranasal co‐administration of rCTB as a mucosal adjuvant with influenza virus HA is necessary not only for the induction of systemic and mucosal HA antibodies, but also for the protection of mice from morbidity and mortality resulting from virus infection.
New serotype of mutans streptococci isolated from pig oral cavityTakada, Kazuko; Igarashi, Mitsuhiko; Yamaguchi, Yasutaka; Hirasawa, Masatomo
doi: 10.1111/j.1348-0421.2008.00014.xpmid: 18380803
Gram‐positive streptococcal mutans‐like strains, but with clearly different colony formation than S. orisuis on Mitis Salivarius agar, were isolated from the pig oral cavity and identified by 16S rRNA sequencing, G+C content, DNA‐DNA homology and extensive biochemical and serological testing. The phenotypic data showed that the strains were similar to S. orisuis except for susceptibility to bacitracin. DNA‐DNA homology between the isolates and S. orisuis was 72∼81%. However, serological data showed that they have a different sero‐specific antigen from S. orisuis and other mutans streptococci. A new serotype, designated p, strains are classified in a serovar of S. orisuis, one of mutans streptococci.
Hsa, an adhesin of Streptococcus gordonii DL1, binds to α2‐3‐linked sialic acid on glycophorin A of the erythrocyte membraneYajima, Ayako; Urano‐Tashiro, Yumiko; Shimazu, Kisaki; Takashima, Eizo; Takahashi, Yukihiro; Konishi, Kiyoshi
doi: 10.1111/j.1348-0421.2008.00015.xpmid: 18380804
Bacterial recognition of host sialic acid‐containing receptors plays an important role in microbial colonization of the human oral cavity. The aggregation of human platelets by Streptococcus gordonii DL1 is implicated in the pathogenesis of infective endocarditis. In addition, we consider that hemagglutination of this organism may act as an additive factor to increase the severity of this disease. We previously reported that this interaction requires the bacterial expression of a 203‐kDa protein (Hsa), which has sialic acid‐binding activity. In the present study, we confirmed that erythrocyte surface sialoglycoproteins are the receptors for Hsa. We examined the effects of proteinase K, chymotrypsin, phospholipase C, and α(2‐3) or α(2‐3, 6, 8) neuraminidase on hemagglutination activity and found that the interaction occurs between Hsa and α2‐3‐linked sialic acid‐containing proteins of erythrocytes. We expressed recombinant NR2, which is the putative binding domain of Hsa, fused with GST in Escherichia coli BL21. Dot‐blot analysis demonstrated that GST‐HsaNR2 binds both glycophorin A (GPA) and band 3. Moreover, GPA and a small amount of band 3 were detected by GST pull‐down assays. These findings indicate that S. gordonii Hsa specifically binds to GPA and band 3, α2‐3‐linked sialic acid membrane glycoproteins.
Human immunodeficiency virus type‐1 vulnerates nascent neuronal cellsKitayama, Hiroko; Miura, Yoshiharu; Ando, Yoshinori; Koyanagi, Yoshio
doi: 10.1111/j.1348-0421.2008.00012.xpmid: 18380805
Macrophages or microglial cells are the major target cells for HIV‐1 infection in the brain. The infected cells release neurotoxic factors that may cause severe neuronal cell damage, especially in the basal ganglia and hippocampus. In this study, we used rat OHC to examine the region‐specific neuronal cell damage caused by HIV‐1‐infected macrophages. When OHC was cocultured with HIV‐1‐infected MDM, we found that neuronal cells at the GCL of the DG were preferentially killed via apoptosis, and that projection of MF from GCL to PCL of the CA3 region was severely disturbed. We marked precursor cells around the DG region by using an EGFP‐expressing retrovirus vector and found that these cells lost the ability to differentiate into neurons when exposed to HIV‐1‐infected MDM. In the DG, new neurons are normally incorporated into GCL or PCL, while in the presence of HIV‐1‐infected MDM, mature neurons failed to be incorporated into those layers. These data indicate that the neurotoxic factor(s) released from HIV‐1‐infected macrophages impede(s) neuronal cell repair in brain tissue. This suggests that DG is the region of the hippocampus most vulnerable to neuronal damage caused by HIV‐1 infection, and that its selective vulnerability is most likely due to the highly active neurogenesis that takes place in this region.
Attenuated Listeria infection activates natural killer cell cytotoxicity to regress melanoma growth in vivoShen, Hua; Kanoh, Makoto; Maruyama, Saho; Matsumoto, Akira; Zhang, Wei; Asano, Yoshihiro
doi: 10.1111/j.1348-0421.2008.00018.xpmid: 18380808
Listeria monocytogenes infection induces various types of immune responses. The Lm‐induced immunity not only protects the hosts against Lm infection but also has a therapeutic effect on other diseases such as tumors and infectious diseases. In the present study, we sought to identify the cells and molecules that are primarily responsible for the Lm‐induced antitumor immune response. We investigated the mechanism of the antitumor immune response induced by Lm infection using melanoma cells and various types of gene‐manipulated mice and B16F10 melanoma cells. Melanoma cells were implanted into mice intrasplenically or intraperitoneally. Lm infection of mice remarkably suppressed the growth of transplanted melanoma. The suppression of melanoma growth was due to the augmented NK cytotoxicity. The Lm‐induced NK activation against melanoma was type I interferon‐ and signal transducer and activator of transcription (STAT)1‐dependent but independent of IL‐12 and IFN‐γ. In contrast to avirulent Listeria innocua and hly− Lm failed to induce NK activation, a mutant Lm strain with minimal hemolytic activity and with normal accessibility to cytoplasm‐induced NK activation. We demonstrated that the attenuated Lm entrance into the cytoplasm induces the production of type I IFN followed by the activation of NK cells, which is essential for the Lm‐induced antitumor response.
The Bordetella type III secretion system: its application to vaccine developmentAbe, Akio; Nagamatsu, Kanna; Watanabe, Mineo
doi: 10.1111/j.1348-0421.2008.00028.xpmid: 18380810
B. pertussis is a causative agent of whooping cough (pertussis) in humans. Despite wide‐scale vaccination in many countries, there is serious concern about pertussis as a re‐emerging disease. Re‐emergence of pertussis may be explained by several factors: the short duration of protection by the currently available acellular pertussis vaccine, an increase in asymptomatic adult carriers and expansion of strains with certain antigenic variations which are not covered by currently available vaccines. To develop safer and more efficacious vaccines which confer more prolonged protection, researchers are focusing on identification and characterization of new virulence factors. One candidate for protective antigens is the type III secretion system and its secreted proteins.