Immunoadjuvant activities of a recombinant chicken IL-12 in chickens vaccinated with Newcastle disease virus recombinant HN protein.
ABSTRACT Recombinant fowlpox virus (rFPV/HN) expressing Newcastle disease virus (NDV) HN gene and rFPV/HN/chIL-12 co-expressing chicken IL-12 (chIL-12) and HN (rHN/chIL-12) genes have been characterized. rHN/chIL-12 or rchIL-12, expressed by our previous construct rFPV/chIL-12, co-administered with rHN was assessed for adjuvant activities of chIL-12. Chickens were vaccinated with various amounts of rHN/chIL-12 mixed with mineral oil (MO), intramuscularly. Levels of hemagglutination-inhibition (HI) antibody production depended on the concentration of the injected rHN or rHN/chIL-12. The lower HI antibody titers were obtained in chicken groups rHN/chIL-12/7-rHN/chIL-12/9, receiving 60ng rHN/8ng chIL-12 with MO, 30ng rHN/4ng chIL-12 with MO or 15ng rHN/2ng chIL-12 with MO, respectively, compared to those in chicken groups rHN/7-rHN/9, receiving rHN with MO alone. However, chickens in group rHN/chIL-12/7 or rHN/chIL-12/8 and rHN with MO alone showed the same effective protection. Chicken group rHN/chIL-12/9 was even more protective than that in group rHN/9. When rchIL-12 was co-injected with 15ng rHN plus MO, chickens produced low levels of HI antibody titers; while higher levels of IFN-γ production and an effective protection rate (83%) were obtained. On the other hand, low levels of IFN-γ production and low protection response (50%) were obtained in chickens injected with rHN with MO alone. Taken together, when the concentration of rHN decreased to certain levels, rchIL-12 reduced HI antibody production. The increase in the induction of IFN-γ production might suggest the enhancement of the cell-mediated immunity which conferred the protection from the NDV challenge.
- SourceAvailable from: washington.edu[Show abstract] [Hide abstract]
ABSTRACT: Adjuvants play an important role in the efficacy of vaccines as the antigens become more and more purified. Indeed recombinant proteins or synthetic peptides are safer than crude inactivated micro-organism, but less immunogenic. This can be balanced by specific adjuvants. But there is no universal adjuvants and their action is not yet clear and rely on different mechanisms. Then, they must be adapted according to several criteria, like the target species, the antigens, the type of immune response, the route of inoculation, or the duration of immunity. For this purpose different type of emulsions have been developed. Water in oil (W/O) emulsions induce a strong and long term immune response. Those based on mineral oils are known to be very efficient but can sometimes induce local reactions with reactive antigens. Non mineral oils are well tolerated but less efficient with poor immunogens. Multiphasic (W/O/W) emulsions can induce short and long term immune responses with various antigens and oil in water (O/W) emulsions are well tolerated and induce a short term immune response. New generation of adjuvants are based on a new concept called 'immunosol' and stem from the association of nanoparticles with a new immunostimulant. They can be used when emulsions are not suitable to obtain a good balance between safety and immunogenicity.Vaccine 04/2001; 19(17-19):2666-72. · 3.49 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Interleukin-12 (IL-12), which is composed of a p35 and a p40 subunit, is a proinflammatory natural-killer (NK) cell-stimulating, Th1-inducing and Th1-maintaining cytokine, which promotes cell-mediated immunity. On activation, heterodimeric IL-12 is found in small amounts, whereas free p40 is produced in excess. Besides IL-12, other p40-dependent molecules exist that orchestrate Th1 responses. Homodimeric p40 can act as an IL-12 antagonist by competing for its receptor. Recent data also reveal potential immunostimulatory functions of p40. In addition, p40 can be covalently linked to a p35-related protein p19. This heterodimer is known as IL-23 and has activities on memory T cells. Finally, IL-27, the latest addition to this family, is a heterodimer composed of the p40-related protein EBI3 (Epstein-Barr virus-induced gene 3) and the p35-related protein p28. IL-27 is involved in early Th1 initiation.Trends in Immunology 05/2003; 24(4):207-12. · 12.03 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The influence of the cytokine interleukin-12 (IL-12) on humoral immune responses was studied in vivo. CBA/J mice immunized with protein antigens (keyhole limpet hemocyanin, phospholipase A2) adsorbed to aluminum hydroxide (Alum) develop a Th2-like immune response characterized by the production of large amounts of IgG1 as well as some IgE but little IgG2a, IgG2b and IgG3 antibodies. IL-12 is a cytokine that promotes the development and the activation of Th1 cells. Th1 cells are involved in the induction of cellular immunity, which is characterized by low or absent antibody production. On the other hand, some Th1-like immune responses are associated with a strong antibody production of the IgG2a, IgG2b and IgG3 subclasses. Thus, we investigated whether treatment with IL-12 would down-regulate the humoral immune response or stimulate antibody production of the IgG2a, IgG2b and IgG3 subclasses. We observed that: 1) administration of IL-12 to mice together with protein antigens adsorbed to Alum strongly enhanced the humoral immune response by increasing the synthesis of antigen-specific antibodies of the IgG2a, IgG2b and IgG3 subclasses 10- to 1000-fold. The synthesis of IgG1 was not or only slightly (2-5-fold) enhanced, whereas that of the IgE isotype was suppressed. 2) These effects of IL-12 were observed when high (10 micrograms, 100 micrograms) or low doses (0.1 microgram) of antigen were used for immunization. 3) Titration of IL-12 in vitro revealed that IgG2a is strongly up-regulated over a wide dose range of IL-12 (10 to 1000 ng/day). 4) The effects of IL-12 in vivo are at least partially interferon (IFN)-gamma-dependent because an anti-IFN-gamma mAb in combination with IL-12 prevented most of the enhanced IgG2a production. 5) Mice receiving IL-12 showed a strong up-regulation of IFN-gamma but no inhibition of IL-5 synthesis by spleen cells activated ex vivo with antigen. These results suggest that IL-12 is a potent adjuvant for enhancing humoral immunity to protein antigens adsorbed to Alum, primarily by inducing the synthesis of the complement-fixing IgG subclasses 2a, 2b and 3.European Journal of Immunology 04/1995; 25(3):823-9. · 4.52 Impact Factor