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Vaccines As Alternatives to Antibiotics for Food Producing Animals

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Vaccines As Alternatives to Antibiotics for Food Producing Animals Vaccines as alternatives to antibiotics for food producing animals. Part 2: new approaches and potential solutions Karin Hoelzer, Lisa Bielke, Damer P. Blake, Eric Cox, Simon M. Cutting, Bert Devriendt, Elisabeth Erlacher-Vindel, Evy Goossens, Kemal Karaca, Stephane Lemiere, et al. To cite this version: Karin Hoelzer, Lisa Bielke, Damer P. Blake, Eric Cox, Simon M. Cutting, et al.. Vaccines as alterna- tives to antibiotics for food producing animals. Part 2: new approaches and potential solutions. Vet- erinary Research, BioMed Central, 2018, 49 (1), pp.70. 10.1186/s13567-018-0561-7. hal-02973513 HAL Id: hal-02973513 https://hal.archives-ouvertes.fr/hal-02973513 Submitted on 21 Oct 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Hoelzer et al. Vet Res (2018) 49:70 https://doi.org/10.1186/s13567-018-0561-7 REVIEW Open Access Vaccines as alternatives to antibiotics for food producing animals. Part 2: new approaches and potential solutions Karin Hoelzer1* , Lisa Bielke2, Damer P. Blake3, Eric Cox4, Simon M. Cutting5, Bert Devriendt4, Elisabeth Erlacher‑Vindel6, Evy Goossens7, Kemal Karaca8, Stephane Lemiere9, Martin Metzner10, Margot Raicek6, Miquel Collell Suriñach11, Nora M. Wong1, Cyril Gay12 and Filip Van Immerseel7 Abstract Vaccines and other alternative products are central to the future success of animal agriculture because they can help minimize the need for antibiotics by preventing and controlling infectious diseases in animal populations. To assess scientifc advancements related to alternatives to antibiotics and provide actionable strategies to support their development, the United States Department of Agriculture, with support from the World Organisation for Animal Health, organized the second International Symposium on Alternatives to Antibiotics. It focused on six key areas: vaccines; microbial-derived products; non-nutritive phytochemicals; immune-related products; chemicals, enzymes, and innovative drugs; and regulatory pathways to enable the development and licensure of alternatives to antibiotics. This article, the second part in a two-part series, highlights new approaches and potential solutions for the develop‑ ment of vaccines as alternatives to antibiotics in food producing animals; opportunities, challenges and needs for the development of such vaccines are discussed in the frst part of this series. As discussed in part 1 of this manuscript, many current vaccines fall short of ideal vaccines in one or more respects. Promising breakthroughs to overcome these limitations include new biotechnology techniques, new oral vaccine approaches, novel adjuvants, new deliv‑ ery strategies based on bacterial spores, and live recombinant vectors; they also include new vaccination strategies in-ovo, and strategies that simultaneously protect against multiple pathogens. However, translating this research into commercial vaccines that efectively reduce the need for antibiotics will require close collaboration among stakehold‑ ers, for instance through public–private partnerships. Targeted research and development investments and concerted eforts by all afected are needed to realize the potential of vaccines to improve animal health, safeguard agricultural productivity, and reduce antibiotic consumption and resulting resistance risks. Table of Contents 2.3 Genetically modifed live microorganisms as oral 1 Introduction vectored vaccines and vaccine platforms 2 New approaches for the development of veterinary 2.4 New approaches for in‑ovo vaccines vaccines 3 Vaccination strategies to reduce antibiotic use for dis‑ 2.1 Mucosal immunity and tolerance: challenges eases from ubiquitous pathogens to the development of efective oral vaccines 3.1 Towards the development of new Clostridium per- 2.2 Recombinant Bacillus spores as oral vectored fringens vaccines vaccines 3.2 Towards the development of new coccidiosis vaccines 3.2.1 Management of coccidiosis through anticoc‑ cidial drugs *Correspondence: [email protected] 1 The Pew Charitable Trusts, 901 E Street NW, Washington, DC 20004, USA 3.2.2 Traditional live anticoccidial vaccines Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat​iveco​mmons​.org/licen​ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat​iveco​mmons​.org/ publi​cdoma​in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Hoelzer et al. Vet Res (2018) 49:70 Page 2 of 15 3.2.3 Next generation anticoccidial vaccines the largest surface area of the body and is exposed daily 4 Autogenous vaccines to reduce the need for antibiotic to vast numbers of foreign antigens derived from feed, use the microbiota and pathogens [1]. Within the intes‑ tine a complex cellular network has evolved to prevent 5 Conclusions unwanted immune responses to innocuous antigens, for References instance feed or microbiota, while allowing swift pro‑ 1 Introduction tective responses against agents that cause infectious Alternatives to antibiotics can help minimize the need disease. Key to keeping enteric pathogens at bay is the for antibiotics by helping to prevent and control infec‑ presence of protective pathogen‑specifc secretory IgA tious diseases in animal populations. As such, safe and (SIgA) at the site of entry, which prevents the adhesion efective alternatives are crucially important to the future of micro‑organisms to the intestinal surfaces and neu‑ success of animal health and production. To assess scien‑ tralizes their enterotoxins. Triggering robust and protec‑ tifc advancements in the research and development of tive intestinal SIgA responses usually requires the local alternatives to antibiotics, highlight promising research administration of vaccines [2]. Although live attenuated results and novel technologies, assess challenges associ‑ oral vaccines have had tremendous success, resulting for ated with their commercialization and use, and provide instance in the near global eradication of poliovirus [3], actionable strategies to support their development, the concerns on the dissemination of vaccine strains into the United States Department of Agriculture (USDA), with environment and rare cases of reversion to virulence, support from the World Organisation for Animal Health leading to vaccine‑induced disease, have driven oral vac‑ (OIE), organized the second International Symposium cine development to nonliving or vectored vaccines [4]. on Alternatives to Antibiotics. Te symposium focused However, oral vaccination is challenging due to several on six key areas: vaccines; microbial‑derived products; hurdles imposed by the cellular and molecular architec‑ non‑nutritive phytochemicals; immune‑related products; ture of the gut: (i) the harsh environment of the stom‑ chemicals, enzymes, and innovative drugs; and regula‑ ach and small intestine, including the low pH, digestive tory pathways to enable the licensure and development of enzymes, and bile salts, required to digest feed also easily alternatives to antibiotics. Tis two‑part manuscript syn‑ destroys vaccines, (ii) a poor uptake of vaccine antigens thesizes and expands on the scientifc presentations and by the intestinal epithelial barrier and (iii) the tolerogenic expert panel discussions from the symposium regard‑ mechanisms that pervade the intestinal tissues, leading to ing the use of vaccines as alternatives to antibiotics that peripheral and oral immune tolerance upon oral admin‑ + can reduce the need for antibiotic use in animals. Part 1 istration of antigens via the induction of FoxP3 regula‑ synthesizes and expands on the expert panel discussions tory T cells. Tis often results in a low immunogenicity of regarding the opportunities, challenges and needs related oral vaccines and requires innovative strategies to deliver to vaccines that may reduce the requirement for use of the vaccine antigens to the intestinal immune system as antibiotics in animals, while part two focuses on high‑ well as the inclusion of adjuvants that promote innate lighting new approaches and potential solutions. and adaptive immunity [5]. A general discussion of the importance of antibiotic Te mucosal immune system in the gut can be divided resistance and the opportunities, challenges and needs in inductive sites, where sampled antigens stimulate naive related to vaccines as alternatives that may reduce the T and B cells, and efector sites, where efector cells per‑ need for use of antibiotics in animals is provided in part form their functions, e.g. assisting in the production of 1 of this review, including a discussion of the proper‑ SIgA. In the small intestine, the inductive sites comprise ties of ideal vaccines, how current
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