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      Veterinary vaccine development from an industrial perspective


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          Veterinary vaccines currently available in Europe and in other parts of the world are developed by the veterinary pharmaceutical industry. The development of a vaccine for veterinary use is an economic endeavour that takes many years. There are many obstacles along the path to the successful development and launch of a vaccine. The industrial development of a vaccine for veterinary use usually starts after the proof of concept that is based on robust academic research. A vaccine can only be made available to the veterinary community once marketing authorisation has been granted by the veterinary authorities.

          This review gives a brief description of the regulatory requirements which have to be fulfilled before a vaccine can be admitted to the market. Vaccines have to be produced in a quality controlled environment to guarantee delivery of a product of consistent quality with well defined animal and consumer safety and efficacy characteristics. The regulatory and manufacturing legislative framework in which the development takes place is described, as well as the trend in developments in production systems. Recent developments in bacterial, viral and parasite vaccine research and development are also addressed and the development of novel adjuvants that use the expanding knowledge of immunology and disease pathology are described.

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          Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus.

          Since it was first described in Australia in 1994, Hendra virus (HeV) has caused two outbreaks of fatal disease in horses and humans, and an isolated fatal horse case. Our preliminary studies revealed a high prevalence of neutralizing antibodies to HeV in bats of the genus PTEROPUS:, but it was unclear whether this was due to infection with HeV or a related virus. We developed the hypothesis that HeV excretion from bats might be related to the birthing process and we targeted the reproductive tract for virus isolation. Three virus isolates were obtained from the uterine fluid and a pool of foetal lung and liver from one grey-headed flying-fox (Pteropus poliocephalus), and from the foetal lung of one black flying-fox (P. alecto). Antigenically, these isolates appeared to be closely related to HeV, returning positive results on immunofluorescent antibody staining and constant-serum varying-virus neutralization tests. Using an HeV-specific oligonucleotide primer pair, genomic sequences of the isolates were amplified. Sequencing of 200 nucleotides in the matrix gene identified that these three isolates were identical to HeV. Isolations were confirmed after RNA extracted from original material was positive for HeV RNA when screened on an HeV Taqman assay. The isolation of HeV from pteropid bats corroborates our earlier serological and epidemiological evidence that they are a natural reservoir host of the virus.
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            Mycobacterium tuberculosis heat shock proteins use diverse Toll-like receptor pathways to activate pro-inflammatory signals.

            Although the Toll-like receptors used by Mycobacterium tuberculosis membrane and secreted factors are known, the pathways activated by M. tuberculosis heat shock proteins are not. An efficient immune response against the intracellular pathogen M. tuberculosis is critically dependent on rapid detection of the invading pathogen by the innate immune system and coordinated activation of the adaptive immune response. Macrophage phagocytosis of M. tuberculosis is accompanied by activation of the transcription factor NF-kappaB and secretion of inflammatory mediators that play an important role in granuloma formation and immune protection during M. tuberculosis infection. The interaction between M. tuberculosis and the various Toll-like receptors is complex, and it appears that distinct mycobacterial components may interact with different members of the Toll-like receptor family. Here we show that recombinant, purified, mycobacterial heat shock proteins 65 and 70 induce NF-kappaB activity in a dose-dependent manner in human endothelial cells. Furthermore, we show that whereas mycobacterial heat shock protein 65 signals exclusively through Toll-like receptor 4, heat shock protein 70 also signals through Toll-like receptor 2. Mycobacterial heat shock protein 65-induced NF-kappaB activation was MyD88-, TIRAP-, TRIF-, and TRAM-dependent and required the presence of MD-2. A better understanding of the recognition of mycobacterial heat shock proteins and their role in the host immune response to the pathogen may open the way to a better understanding of the immunological processes induced by this important human pathogen and the host-pathogen interactions and may help in the rational design of more effective vaccines or vaccine adjuvants.
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              Anticoccidial vaccines for broiler chickens: pathways to success.

              The use of live vaccines, either attenuated or non-attenuated, for the control of coccidiosis due to Eimeria infections in broiler breeder or layer chickens is well established. Use in broilers, however, has been slow to gain acceptance. This has been partly for economic reasons, but also because of perceived adverse effects on early chick growth, particularly with non-attenuated vaccines, and concerns about timely onset of protective immunity in such short-lived birds. This review describes advances in understanding of epidemiological factors and recent improvements of administration methods that have helped to allay these fears and to make the use of anticoccidial vaccines in broilers technically achievable. Topics discussed include: (1) types of commercially available vaccine, (2) vaccines in development, (3) vaccination methods and equipment, (4) basis of vaccine efficacy and immunogenic variation of parasites, (5) key factors in the survival, sporulation and dissemination of vaccinal oocysts, (6) descriptions and significance of patterns of litter oocyst accumulation and occurrence of intestinal lesions in vaccinated flocks, (7) rotation of anticoccidial vaccination and chemotherapy to restore drug sensitivity to resistant wild-type coccidia, (8) combinations of anticoccidial vaccination and chemotherapy, (9) interactions between coccidiosis and clostridiosis in broilers and compatibilities of potential control methods, (10) published performance data for live anticoccidial vaccines in broilers, (11) possible further developments of live vaccines.

                Author and article information

                Vet J
                Vet. J
                Veterinary Journal (London, England : 1997)
                Elsevier Ltd.
                3 March 2008
                October 2008
                3 March 2008
                : 178
                : 1
                : 7-20
                [a ]Department for Virological R&D, Nobilon International BV, Exportstraat 39b, 5830 AH Boxmeer, The Netherlands
                [b ]JAS Biologicals Ltd., The Annex, Innes Building, The Centre for Veterinary Science, Madingley Road, CB3 0ES Cambridge, UK
                [c ]Department for Bacteriological R&D, Intervet International BV, Milton Keynes, UK
                [d ]Department for Regulatory Affairs, Intervet International BV, W. de Körverstraat 35, 5831 AN Boxmeer, The Netherlands
                [e ]Department for Vaccine Technology and Immunology, Intervet International BV, W. de Körverstraat 35, 5831 AN Boxmeer, The Netherlands
                [f ]Department for Quality Operations, Nobilon International BV, Exportstraat 39b, 5830 AH Boxmeer, The Netherlands
                [g ]Department for Parasitological R&D, Intervet International BV, W. de Körverstraat 35, 5831 AN Boxmeer, The Netherlands
                Author notes
                [* ]Corresponding author. Tel.: +31 485 585232; fax: +31 485 585445. jacco.heldens@ 123456nobilonvaccines.com
                Copyright © 2007 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                : 12 November 2007

                Veterinary medicine
                vaccine,industry,regulatory,good manufacturing practice (gmp)
                Veterinary medicine
                vaccine, industry, regulatory, good manufacturing practice (gmp)


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