Anti-IL-4 Anticorps [BVD6-24G2] (Biotin) (A269776)

We previously demonstrated that intramuscular immunization with virus-like particles (VLPs) composed of the haemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of A/meerkat/Shanghai/SH-1/2012 (clade 2.3.2.1) protected mice from lethal challenge with viruses from other H5 HPAI clades. The inclusion of additional proteins that can serve as immunological adjuvants in VLPs may enhance adaptive immune responses following vaccination, and oral vaccines may represent the safest choice. Here, we report the generation of H5N1 VLPs composed of the viral HA, NA, and M1 proteins and membrane-anchored forms of the Escherichia coli heat-labile enterotoxin B subunit protein (LTB) or the Toll-like receptor 5 ligand flagellin (Flic). Mice intramuscularly or orally immunized with VLPs containing LTB or Flic generated greater humoural and cellular immune responses than those administered H5N1 VLPs without LTB or Flic. Intramuscular immunization with VLPs protected mice from lethal challenge with homologous or heterologous H5N1 viruses irrespective of whether the VLPs additionally included LTB or Flic. In contrast, oral immunization of mice with LTB- or Flic-VLPs conferred substantial protection against lethal challenge with both homologous and heterologous H5N1 influenza viruses, whereas mice immunized orally with VLPs lacking LTB and Flic universally succumbed to infection. Mice immunized orally with LTB- or Flic-VLPs showed 10-fold higher virus-specific IgG titres than mice immunized with H5N1-VLPs lacking LTB or Flic. Collectively, these results indicate that the inclusion of immunostimulatory proteins, such as LTB and Flic, in VLP-based vaccines may represent a promising new approach for the control of current H5N1 HPAI outbreaks by eliciting higher humoural and cellular immune responses and conferring improved cross-clade protection.

Propranolol (Pro), a non-specific ß-adrenergic blocking drug, competitively prevents the binding of catecholamines to receptors and suppresses cancer cells. The anti-tumor activity of propranolol has been proved in different kinds of cancers. In this study, we assessed the adjuvant activity of propranolol combined with a tumor vaccine model on the immunological parameters of breast tumor-bearing mice. Breast tumor pieces were implanted into the flank of inbred BALB/C female mice from stock mice. Tumor-bearing mice were treated with tumor antigen lysate vaccine and propranolol/Vaccine (Pro/Vac) combination (as treatment groups), propranolol and PBS (as control groups) for 5 consecutive days, every 12 h. Moreover, all experimental groups received vaccine for three times with one-week interval via s.c injection. After immunization courses, spleens of tumor-bearing mice were removed and dissected, cell suspension was stimulated in vitro, and the cytokine levels in supernatant of splenocytes were measured via commercial ELISA kits. Compared with the vaccine group, immunization with tumor lysate in combination with propranolol significantly increased IL-2, IL-4, IL-12, IL-17, and IFN-? cytokines. Considering the suppression of tumor growth, propranolol seems to be a potent immunomodulator capable of inducing cellular immune responses against breast cancer.

A preferred adjuvant should promote both Th1 and Th2 responses. However, most adjuvants in common use are biased towards a Th2-driven response. Therefore, the ability of a novel saponin-based adjuvant G3 to inducing balanced Th1 and Th2 responses in BALB/c mice immunized with a split trivalent seasonal influenza vaccine was evaluated in comparison to that of the adjuvant Al(OH)₃. Clear differences in the IgG profiles induced by G3, Al(OH)₃ or non-adjuvanted vaccine were recorded. Both adjuvants enhanced high and similar levels of the Th2 associated IgG1 subtype compared to mice given vaccine alone. Only G3 enhanced the IgG2a subclass reflecting a Th1 response, whereas Al(OH)₃ even abrogated the IgG2a production. Accordingly, G3 enhanced the production of IL-2 and IFN-? and also of IL-2/IFN-? double secreting cells, emphasizing the strong Th1 driving effect of G3. Only Al(OH)₃ increased splenocyte production of IL-17. Taken together, the results indicate a strong propensity for G3 to induce both Th1 and Th2 driven immune responses.

Modern vaccines based on purified recombinant antigens have improved their safety; however they induce a suboptimal immune response without the help of adjuvants. Consequently, the development of new adjuvants to enhance the immunogenicity of purified subunit antigens and modulate resulting immune responses is of great interest. In the present study, we evaluated the ability of antimicrobial peptides Oreochromicins previously isolated from tilapia Oreochromis niloticus to enhance adaptive immune responses in mice and tilapia. When co-administrated with ovalbumin in mice, Oreochromicin-1 induced a TH1 humoral immune response. Oreochromicin-2 and 3 induce a TH1 cellular immune response characterized by the induction of interferon-? in a dose depend manner. Additionally, co-administration of Oreochromicin-1 with the sea lice my32 from Lepeophtheirus salmonis antigen (my32-Ls) increases the humoral immune response in mice and tilapia. We also tested different combinations of these Oreochromicins with the sea lice antigen my32-Ls in mice. Humoral and cellular TH1 responses were enhanced by co-administration of my32-Ls/Oreochromicin-3 and the combination my32-Ls/Oreochromicin-2/3. In agreement with these results, Oreochromicin-1 and 3 enhanced in vitro TH1 cytokine IFN-? production in Concanavalin A primed splenocytes from naïve mice after a 48h incubation period. In summary, the results showed that tilapia alpha-helical antimicrobial peptides Oreochromicins are able to boost immune response in mammals and fish, encouraging their use as TH1 molecular adjuvants to subunit antigens.

Immunoglobulin class switching from IgM to IgG in response to peptides is generally T cell-dependent and vaccination in T cell-deficient individuals is inefficient. We show that a vaccine consisting of a dense array of peptides on liposomes induced peptide-specific IgG responses totally independent of T-cell help. Independency was confirmed in mice lacking T cells and in mice deficient for MHC class II, CD40L, and CD28. The IgG titers were high, long-lived, and comparable with titers obtained in wild-type animals, and the antibody response was associated with germinal center formation, expression of activation-induced cytidine deaminase, and affinity maturation. The T cell-independent (TI) IgG response was strictly dependent on ligation of TLR4 receptors on B cells, and concomitant TLR4 and cognate B-cell receptor stimulation was required on a single-cell level. Surprisingly, the IgG class switch was mediated by TIR-domain-containing adapter inducing interferon-ß (TRIF), but not by MyD88. This study demonstrates that peptides can induce TI isotype switching when antigen and TLR ligand are assembled and appropriately presented directly to B lymphocytes. A TI vaccine could enable efficient prophylactic and therapeutic vaccination of patients with T-cell deficiencies and find application in diseases where induction of T-cell responses contraindicates vaccination, for example, in Alzheimer disease.