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® with ® The NEW COMBINED VACCINE against neonatal diarrhoea in piglets and sudden death in sows Experience a new type of immunity! ® The guidelines on the development of new adjuvants play a d between the non-specific immune respon HIPRAMUNE®-G is the new a based on saponins e extracted f Non-specific Immune response Ginsenosidess Attract and stimulate the production and maturation of mononuclear cells, dendritic cells and macrophages 8,9. Light Ginsenosides induce the Ginsenosides capturee of the antigen Rough endoplasmic reticulum Antigen/ginsenoside The antigen, dendritic cells and macrophages, presenting cells are responsible for capturing the antigen and presenting it to the rest of the immunological system. Nucleus Transporter MHC class I Golgi complex MHC class I molecule Immunohistocompatibility I complex Cytotoxic cells/NK Dendritic cell ® is the first vaccine marketed that includes this Light and potent determining role in the mediation and establishment of a link nse and the adaptive immune response6. adjuvant developed by HIPRA rom GINSENG: GIN GINSENOSIDES Immunological studies conducted at the HIPRA R&D Department have demonstrated that HIPRAMUNE®-G: Lynphatic vessel ■ Stimulates production of peripheral mononuclear cells (this cell population is key at the inoculation site of a vaccine for giving a proper immunological response). Lymphatic ganglia The combination of a water-based adj adjuvant (aluminium hydroxide) and ginsenosid ginsenosides modulates the cellular and humoral response, thereby inducing improved protection9. T-helper cell ■ Stimulates the maturation of dendritic cells, thereby improving an animal’s antigen presentation process. Potent MHC class II Immunohistocompatibility II complex Adaptative Immune Response MHC class II molecule Lymphocyte B/Plasmatic cell T-helper cell A water-based adjuvant with ginsenosides increases production of antibodies in comparison with conventional water-based adjuvants10. Cytotoxic T cellsNK innovative technology: ® with ® Efficaciously induces antibody production L IGHT Greater vaccinal safety Thanks to its new g generation water-based adjuvant, : ® Forget about lumps on the neck! Does not produce FEVER Does not have ADVERSE REACTIONS Does not cause LUMPS at the inoculation site The safest vaccine An experimental study conducted with SUISENG® and the leading vaccines marketed for preventing neonatal diarrheoa assessed their SAFETY. The results demonstrated that SUISENG® was the safest vaccine in the test. Progress of rectal temperatures in each treatment group VACCINATION REVACCINA REVACCINATION 41,00 40,50 40,00 39,50 39,00 Day 1 Day 0 Day 0 +2h Day 0 +4h Day 0 +6h Day 1 Day 2 Day 3 Day 20 Vaccination Day 21 Day 21 +2h Day 21 +4h Day 21 +6h Day 22 Day 23 Day 24 Revaccination ■ SUISENG® ■ Vaccine 1 (5 ml/dose with AI (OH)3 ■ Vaccine 2 (2 ml/dose with α-Tocoferol) ■ Placebo Percentage of animals that showed some general or local sign after administration of the treatments VACCINATION REVACCINATION 62,5 General signs: fever, depression and listlessness. * 75,0 * 62,5 50,0 * 37,5 25,0 Local signs: inflammatory reaction at inoculation site. 0 0 % General signs 0 12,5 0 % Local signs 0 0 % General signs 0 12,5 % Local signs * There are significant differences compared to the SUISENG® group. Optimal vaccinal safety with a light and potent adjuvant: ® 12,5 POTENT Better protection improved protection against neonatal diarrheoa under experimental conditions* * In comparison with another water-based combined vaccine against E. coli and Cl. perfringens The potency of SUISENG® is demonstrated in a challenge trial with E. coli1 Three groups of 1-day-old piglets were chosen that had properly ingested colostrum and they were challenged with a strain of enteropathogenic E. coli. Non-vaccinated control Commercial vaccine (5 ml/dose) SUISENG® (2 ml/dose) 65,0 65,0 % of diarrhoea and mortality in the first week of life 37,5 35,3 32,4 14,7 3,4 % Mortality 13,8 10,3 % Diarrhoea a Morbidity (% Diarrhoea and/or Mortality) HYPERIMMUNIZATION of the colostrum demonstrated! Well immunised colostrum in the first week of life is fundamental for preventing the incidence of diarrhoea in the farrowing pen HIPRA’s R&D services conducted a study2 in NULLIPAROUS animals to assess quantitatively and qualitatively the production of specific antibodies against the main adhesion factors of the strains of E. coli and the β toxin of Cl. perfringens in the colostrum of sows. Hyperimmunization against E. coli The findings demonstrate SUISENG®’s capacity for hyperimmunisation of colostrum against neonatal colibacillosis. Antibody titres in piglets 12 hours post-partum SUISENG® Placebo LT 65,8 31,3 F4 ab 114,9 38,7 F4 ac 93,5 17,3 F6 68,3 4,4 F5 30,3 10,9 Hyperimmunzation against necrotic enteritis in piglets (Cl. perfringens type C) Titres of neutralising antibodies of the type C Cl. perfringens β toxin higher than 5IU/ml of colostrum significantly prevent the mortality caused by necrotic enteritis in litters of piglets3. CONTROL Titres >5 UI/ml Titres: 0 UI/ml The most complete vaccine: TRIPLE protection is the only vaccine that prevents neonatal diarrheoa in piglets caused by E. coli and Cl. perfringens type C and neutralises the α toxin of Clostridium novyi responsible for sudden death in sows sudden death of lactating sows caused by Clostridium novyi Clostridium novyi types A and B is a Gram-positive anaerobic bacterium. Acute infection caused by it is considered the most significant cause of mortality in breeder sows11,12,13. SUDDEN DEATH of sows is a problem that mainly affects sows in the last trimester of gestation and LACTATING BREEDERS12,13. α α α α α α α α α α Cl. Novyi ’s pathogenesis is mediated by the lethal necrotising α TOXIN. α toxin Systemic dissemination of the α TOXIN produces cardio, neuro, histo and hepatotoxic effects that result in ACUTE or HYPERACUTE DEATH11. Reduction of the farm productivity Elevated mortality Increase of the replacement rate TRIPLE protection: ■ Neonatal diarrhoea caused by E. coli ■ Necrotic enteritis of piglets caused by Cl. perfringens ■ Neutralization of the Cl. Novyi α toxin Efficaciously induces serum neutralising antibodies against the α toxin HIPRA’s R&D Department assessed the capacity to induce SERUM NEUTRALISING ANTIBODIES against the α TOXIN of Clostridium novyi in breeder sows vaccinated with SUISENG®. CONTROL Physiologic Solution α α α 1 2 3 α Toxin 1 2 3 They collected serum from sows vaccinated with SUISENG®, and sows inoculated with physiological serum were maintained as a CONTROL group at the time of farrowing (3 weeks after the 2nd vaccination). These sera were mixed with the purified α TOXIN of Cl. novyi. α α α They were inoculated in mice to assess the mortality induced by the toxin. The findings demonstrated the capacity of the sera of the sows vaccinated with SUISENG® to neutralise TOXIN. α 4 100% alive 100% dead SUISENG PROTECTS B REEDER SOWS ® AND THEIR RP PIGLETS IGLETS ® ® with A MORE COMPLETE, EFFICACIOUS AND SAFE VACCINE ■ ■ ■ ■ ■ ■ Light and potent Better protection against neonatal diarrhoea caused by E. coli and Clostridium perfringens type C Greater antigenic spectrum Neutralizes the Clostridium novyi α toxin responsible for SUDDEN DEATH in lactating sows Protection of breeder sows and their piglets Maximum safety 1. Estudio PE-05-CB-25. 2. Estudio PE-06-09. 3. Ripley PH, Gush AF. “Immunisation Schedule for the prevention of infectious necrotic enteritis caused by Clostridium perfringens type C in piglets”. Vet REc. 1983 Feb 26;112 (9): 201-2. 4. Estudio PE-06-CB-18. 5. Estudio PE-05-CB-31. 6. Garlapati, S., M. Facci, M. Polewicz, S. Strom, L.A. Babiuk, G. Mutwiri, R.E. Hancock, M.R. Elliott, and V. Gerdts. Strategies to link innate and adaptive immunity when designing vaccine adjuvants. Vet. Immunol. Immunopathol. 2008. 7. Masao Takei, Eiichi Tachikawa, Hideo Hasegawa, Je-Jung Lee. “Dendritic cells maduration promoted by M1 and M4 end products of steroideal ginseng saponings metabolized in digestive tracts, drive a potent TH1 polaritation”. Bioch. Pharmacology 68 (2004). 441-452. 8. Rajput, Z.I., S.H. Hu, C.W. Xiao, and A.G. Arijo. Adjuvant effects of saponins on animal immune responses. J. Zhejiang. Univ Sci. B. 8:153-161. 2007. 9. Sun, Y., H. Tong, M. Li, Y. Li, S. Guan, and J. Liu. Immunological adjuvant effect of Japanese ginseng saponins (JGS) on specific antibody and cellular response to ovalbumin and its haemolytic activities. Vaccine. 2008. 10. Rivera, E., A. Daggfeldt, and S. Hu. Ginseng extract in aluminium hydroxide adjuvanted vaccines improves the antibody response of pigs to porcine parvovirus and Erysipelothrix rhusiopathiae. Vet. Immunol. Immunopathol. 91:19-27. 2003. 11. Itoh, H; Uchida, M.; Sugiura, H.; Ogusu, S.; Yamakawa, K. “Outbreak of Clostridium novyi infection in swine and its rapid diagnosis Journal of the Japanese Veterinary Medical Association (1983) 40:365-369. 12. Duran, CO.; Walton, JR. “Clostridium novyi sudden death in sows: toxemia o post mortem invader? Pig Journal 39:7-53 (1987). 13. Shultz, RAet al. (2001) A sow mortality study-the real reasons sows die: identigying causes and implementing action. Proc Am Assoc Swine Vet. 387-395. SUISENG®: COMPOSITION PER DOSE (2 ml): F4ab fimbrial adhesin of E. coli ≥ 65% ER60*; F4ac fimbrial adhesin of E. coli ≥78% ER70; F5 fimbrial adhesin of E. coli ≥ 79% ER50; F6 fimbrial adhesin of E. coli ≥ 80% ER25; LT Enterotoxoid of E. coli ≥ 55% ER70; Toxoid Clostridium perfringens, type C ≥ 35% ER25. Toxoid Clostridium novyi ≥ 50% ER120 *% ERx: Percentage of immunized rabbits with a X serological EIA response. Adjuvant based on Aluminium hydroxide and Ginseng extract. INDICATIONS: Swine: For the passive protection of neonatal piglets by means of the active immunisation of breeding sows and gilts to reduce mortality and clinical signs of neonatal enterotoxicosis and Necrotic Enteritis. For active immunisation of breeding sows and gilts to induce seroneutralizing antibodies against α-toxin of Clostridium novyi. Laboratorios Hipra, S.A. Avda. la Selva, 135 17170 Amer (Girona) Spain ADMINISTRATION ROUTE: Intramuscular, into the neck muscles. Basic vaccination Revaccination 1st dose 2nd dose 6 weeks 3 weeks 1st dose FARROWING 6 weeks 3 weeks FARROWING Swine: 2 ml/animal. The basic vaccination scheme consists of two doses: the first dose at approximately 6 weeks before farrowing and a second dose at approximately 3 weeks before farrowing. Revaccination: on each subsequent gestation, administer one dose 3 weeks before the expected date of farrowing. WITHDRAWAL PERIOD: 0 days. SPECIAL PRECAUTIONS: Store and transport refrigerated (2 ºC and 8 ºC). Protect from light. Do not freeze. PACKAGING: 1 vial of 10 ds, 1 vial of 25 ds, 1 vial of 50 ds. Under veterinary prescription. FOR VETERINARY USE ONLY. Reg. Nº: 2085 ESP. Tel. (34) 972 43 06 60 Fax (34) 972 43 06 61 [email protected] www.hipra.com