Periodic Reporting for period 3 - SAPHIR (Strengthening Animal Production and Health through the Immune Response)
Période du rapport: 2018-03-01 au 2019-02-28
The animal production sector suffers from important economic losses due to endemic infectious diseases, which hamper profitability, alter animal welfare, and lead to antimicrobial use with environmental and public health consequences. Vaccination integrated in a global health management system is a sustainable, ethical and efficient preventive strategy. However, many commercial vaccines are less than effective in the field or are simply not available. In the SAPHIR project, our goal was to develop animal vaccines against six major livestock pathogens: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Mycoplasma (M.) hyopneumoniae in pigs, Eimeria species (E.) and Clostridium (C.) perfringens in chickens, Bovine Respiratory Syncytial Virus (BRSV) and Mycoplasma (M.) bovis in cattle.
The fulfilled SAPHIR objectives are:
- an improved understanding the socio-economic impact of SAPHIR diseases, of the drivers of vaccine use, of the expected socio-economic benefits of SAPHIR vaccines
- the development of pathogen-specific vaccines
- the development of generic strategies for SAPHIR pathogens and also adaptable to many others, including identification of markers of immunocompetence for adapting breeding to vaccination, new adjuvants, vector vaccines, delivery methods and strategies optimised for young-aged animals.
- the translation of research into field by optimizing route to market and vaccine use
- the dissemination, outreach and training by communication events, web tools, meetings and invitations of stakeholders, and courses to animal health professionals.
The fulfilled SAPHIR objectives are:
- an improved understanding the socio-economic impact of SAPHIR diseases, of the drivers of vaccine use, of the expected socio-economic benefits of SAPHIR vaccines
- the development of pathogen-specific vaccines
- the development of generic strategies for SAPHIR pathogens and also adaptable to many others, including identification of markers of immunocompetence for adapting breeding to vaccination, new adjuvants, vector vaccines, delivery methods and strategies optimised for young-aged animals.
- the translation of research into field by optimizing route to market and vaccine use
- the dissemination, outreach and training by communication events, web tools, meetings and invitations of stakeholders, and courses to animal health professionals.
The results of the SAPHIR project are:
1) The productivity reductions due to bovine respiratory disease (covering BRSV and M. bovis) and of Eimeria infection in European broiler production systems were estimated to be around 5%. The loss due to PRRSV in a typical European farrow-to-finish farm was estimated to reach €400/sow/year .
2) Vaccine use depends on the perception of farmers, food industry, and consumers. Visual evidence of efficacy, time, effort, public acceptance, effects on sales and incomes and reliability of vaccine supply are important factors in the adoption of vaccines on-farm. In the beef cattle sector, the use of vaccines by breeders will certainly require the introduction of a premium for vaccinated calves.
3) Pathogen-specific vaccines:
- PRRSV: a new attenuated vaccine showing protective efficacy against a distant strain was licensed to industry. The mutations allowing derivation of attenuated vaccines from new strains were identified. A DNA prime-boost with attenuated vaccine was identified as an immuno-potentiating strategy, for broader coverage. Progresses towards a vaccine with a companion test differentiating the infected from vaccinated animals (DIVA) were made.
- M. hyopneumoniae: a bacterin vaccine, administered with squalene and TLR ligands, showed strong protective efficacy and safety. An attenuated vaccine, showing some efficacy, was developed.
- Eimeria: transgenic Eimeria parasites, delivering heterologous proteins from other strains, induced significant cross-protection. This strategy reduces the cost of current commercial formulations.
- M. bovis: conserved proteins, inducing strong humoral and cellular immunity, were generated for a subunit vaccine.
- C. perfringens: bacilli expressing conserved proteins were generated and used as an oral vaccine in chicken.
- BRSV: a one-shot subunit vaccine, with high safety profile, induced a high level of protection in calves with maternal antibodies, superior to a commercial vaccine. The biomarkers of vaccine efficacy were identified. A DIVA companion test was developed. Patents are held by SAPHIR partners.
4) Generic vaccine strategies:
- defined immunostimulatory adjuvants (TLR, STING, Mincle ligands) presented variable efficacy depending on the inactivated vaccine used, the route, the species and the age of the animals.
- skin patches loaded with PRRSV-DNA and inactivated PRRSV vaccines, as well as nasal administration of bacterin, were less effective than systemic administration. PRRSV-DNA vaccination with needle-free jet delivery revealed to be very promising.
- genetic polymorphism and transcriptomic signatures have been obtained from leukocytes of large cohorts of chicken and pigs presenting high and low responses to vaccines. Open arrays were built as validation tools.
5) Epidemiological modeling: prophylactic mass vaccination with PRRSV vaccine was predicted to be potently effective even with an incomplete/imperfect vaccine, whereas one-off vaccination has limited effect. Monovalent vaccine use affect the genetic of circulating strains.
6) Dissemination and training were implemented through an active SAPHIR public website and Twitter, newsletters, published papers, meeting with stakeholders shared with Feed-a-Gene-H2020, an integrated health strategies website and training workshops shared with the PARAGONE-H2020 project and the UK Veterinary Vaccinology Networks.
So far, the dissemination encompasses: 20 published papers, 37 posters, 71 oral communications, 17 SAPHIR-organised conferences/workshops, and many more to come.
1) The productivity reductions due to bovine respiratory disease (covering BRSV and M. bovis) and of Eimeria infection in European broiler production systems were estimated to be around 5%. The loss due to PRRSV in a typical European farrow-to-finish farm was estimated to reach €400/sow/year .
2) Vaccine use depends on the perception of farmers, food industry, and consumers. Visual evidence of efficacy, time, effort, public acceptance, effects on sales and incomes and reliability of vaccine supply are important factors in the adoption of vaccines on-farm. In the beef cattle sector, the use of vaccines by breeders will certainly require the introduction of a premium for vaccinated calves.
3) Pathogen-specific vaccines:
- PRRSV: a new attenuated vaccine showing protective efficacy against a distant strain was licensed to industry. The mutations allowing derivation of attenuated vaccines from new strains were identified. A DNA prime-boost with attenuated vaccine was identified as an immuno-potentiating strategy, for broader coverage. Progresses towards a vaccine with a companion test differentiating the infected from vaccinated animals (DIVA) were made.
- M. hyopneumoniae: a bacterin vaccine, administered with squalene and TLR ligands, showed strong protective efficacy and safety. An attenuated vaccine, showing some efficacy, was developed.
- Eimeria: transgenic Eimeria parasites, delivering heterologous proteins from other strains, induced significant cross-protection. This strategy reduces the cost of current commercial formulations.
- M. bovis: conserved proteins, inducing strong humoral and cellular immunity, were generated for a subunit vaccine.
- C. perfringens: bacilli expressing conserved proteins were generated and used as an oral vaccine in chicken.
- BRSV: a one-shot subunit vaccine, with high safety profile, induced a high level of protection in calves with maternal antibodies, superior to a commercial vaccine. The biomarkers of vaccine efficacy were identified. A DIVA companion test was developed. Patents are held by SAPHIR partners.
4) Generic vaccine strategies:
- defined immunostimulatory adjuvants (TLR, STING, Mincle ligands) presented variable efficacy depending on the inactivated vaccine used, the route, the species and the age of the animals.
- skin patches loaded with PRRSV-DNA and inactivated PRRSV vaccines, as well as nasal administration of bacterin, were less effective than systemic administration. PRRSV-DNA vaccination with needle-free jet delivery revealed to be very promising.
- genetic polymorphism and transcriptomic signatures have been obtained from leukocytes of large cohorts of chicken and pigs presenting high and low responses to vaccines. Open arrays were built as validation tools.
5) Epidemiological modeling: prophylactic mass vaccination with PRRSV vaccine was predicted to be potently effective even with an incomplete/imperfect vaccine, whereas one-off vaccination has limited effect. Monovalent vaccine use affect the genetic of circulating strains.
6) Dissemination and training were implemented through an active SAPHIR public website and Twitter, newsletters, published papers, meeting with stakeholders shared with Feed-a-Gene-H2020, an integrated health strategies website and training workshops shared with the PARAGONE-H2020 project and the UK Veterinary Vaccinology Networks.
So far, the dissemination encompasses: 20 published papers, 37 posters, 71 oral communications, 17 SAPHIR-organised conferences/workshops, and many more to come.
The SAPHIR expected impacts benefit to:
- public health and decreasing antibiotic resistance. The vaccine strategies (specific vaccines, adjuvant-mediated trained immunity, immunocompetence) will lead to better control of primary or secondary infectious diseases and thus decrease antimicrobial/antibiotic use.
- efficiency and profitability of the animal production sector. Reduction of animal diseases with vaccines will increase the economic margins, though improving the feed conversion ratio and reducing the cost of treatments. The profitability of novel vaccines depends on their relative efficacy and cost compared to existing control measures. Thresholds of profitability were established through economic modeling. With the reduction of antimicrobials use through market pressure and/or legislative measures, the SAPHIR vaccines will be necessary to sustain the production of the animal sector.
- breeding companies. The genetic markers and biomarkers of immunocompetence will be useful for marker-assisted breeding.
- pharmaceutical industry. Proof of concept were provided for vaccines and adjuvants responding to unmet needs (all SAPHIR pathogens).
- diagnostic industry. The DIVA test established as companion to BRSV subunit vaccine should interest this industry.
- animal welfare. Vaccines and improved breeds will reduce death and suffering from endemic infectious diseases, especially in the context of antimicrobial use reduction or ban.
- societal acceptance. Vaccine use depends on efficacy, availability and cost compared to other control methods, on the extra work burden and ease of administration, on the absence of needed repetition. Vaccines developed in SAPHIR aim at social acceptance (one shot BRSV vaccine, lower-price Eimeria vaccine)
- public health and decreasing antibiotic resistance. The vaccine strategies (specific vaccines, adjuvant-mediated trained immunity, immunocompetence) will lead to better control of primary or secondary infectious diseases and thus decrease antimicrobial/antibiotic use.
- efficiency and profitability of the animal production sector. Reduction of animal diseases with vaccines will increase the economic margins, though improving the feed conversion ratio and reducing the cost of treatments. The profitability of novel vaccines depends on their relative efficacy and cost compared to existing control measures. Thresholds of profitability were established through economic modeling. With the reduction of antimicrobials use through market pressure and/or legislative measures, the SAPHIR vaccines will be necessary to sustain the production of the animal sector.
- breeding companies. The genetic markers and biomarkers of immunocompetence will be useful for marker-assisted breeding.
- pharmaceutical industry. Proof of concept were provided for vaccines and adjuvants responding to unmet needs (all SAPHIR pathogens).
- diagnostic industry. The DIVA test established as companion to BRSV subunit vaccine should interest this industry.
- animal welfare. Vaccines and improved breeds will reduce death and suffering from endemic infectious diseases, especially in the context of antimicrobial use reduction or ban.
- societal acceptance. Vaccine use depends on efficacy, availability and cost compared to other control methods, on the extra work burden and ease of administration, on the absence of needed repetition. Vaccines developed in SAPHIR aim at social acceptance (one shot BRSV vaccine, lower-price Eimeria vaccine)