Hoelzer et al. Vet Res (2018) 49:64 https://doi.org/10.1186/s13567-018-0560-8 REVIEW Open Access Vaccines as alternatives to antibiotics for food producing animals. Part 1: challenges and needs 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 can help minimize the need for antibiotics by preventing and controlling infectious diseases in animal populations, and are central to the future success of animal agriculture. To assess scien‑ tifc advancements related to alternatives to antibiotics and provide actionable strategies to support their develop‑ ment, 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, part of a two-part series, synthesizes and expands on the expert panel discussions regarding opportuni‑ ties, challenges and needs for the development of vaccines that may reduce the need for use of antibiotics in animals; new approaches and potential solutions will be discussed in part 2 of this series. Vaccines are widely used to prevent infections in food animals. Various studies have demonstrated that their animal agricultural use can lead to signifcant reductions in antibiotic consumption, making them promising alternatives to antibiotics. To be widely used in food producing animals, vaccines have to be safe, efective, easy to use, and cost-efective. Many current vaccines fall short in one or more of these respects. Scientifc advancements may allow many of these limitations to be overcome, but progress is funding-dependent. Research will have to be prioritized to ensure scarce public resources are dedicated to areas of potentially greatest impact frst, and private investments into vaccine development constantly compete with other investment opportunities. Although vaccines have the potential to improve animal health, safeguard agricul‑ tural productivity, and reduce antibiotic consumption and resulting resistance risks, targeted research and develop‑ ment investments and concerted eforts by all afected are needed to realize that potential. Table of Contents 5 Investment decision‑making in the research and devel‑ 1 Introduction opment of veterinary vaccines 2 Vaccines as alternatives to antibiotics 6 Prioritization of diseases for which vaccines can 3 Properties of current vaccines reduce antibiotic use 4 Limitations of current vaccines as alternatives 7 Conclusions to antibiotics References *Correspondence: [email protected] 1 The Pew Charitable Trusts, 901 E Street NW, Washington, DC 20004, USA 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) 49:64 Page 2 of 10 1 Introduction were ranked highest for perceived feasibility and among Antibiotic resistance is a global threat to public health [1–4]. the top fve alternative approaches with regard to per‑ Every time an antibiotic is used in any setting, there is a risk ceived efectiveness [10]. A quasi‑experimental study of of selecting for resistant bacterial strains [2, 4–6]. Terefore, farrow‑to‑fnish pig farms in Belgium has demonstrated prudent or judicious antibiotic use is important [7]. In ani‑ the cost‑efectiveness of enhanced biosecurity and vac‑ mal agricultural production, that means using antibiotics cinations to reduce antibiotic consumption [11]. Simi‑ only when absolutely necessary to protect the health of the larly, the implementation of herd‑specifc action plans animal and/or humans, relying on non‑antibiotic alternatives that included improvements in vaccination on pig opera‑ to manage animal health where possible, and making opti‑ tions in Belgium led to reduced antimicrobial consump‑ mal treatment choices with regard to antibiotic drug selec‑ tion and improvements in production parameters such as tion and treatment protocol when antibiotics are needed. mortality rates and daily weight gains [12]. Alternatives to antibiotics can help minimize the need for A variety of studies have demonstrated that the use of antibiotics by helping to prevent and control infectious dis‑ various bacterial as well as viral vaccines in animal popu‑ eases in animal populations. As such, safe and efective lations can result in a signifcant reduction in antibiotic alternatives are crucially important to the future success of consumption [13]. For example, the introduction and animal health and production. To assess scientifc advance‑ widespread routine use of a vaccine against Aeromonas ments in the research and development of alternatives to salmonicida led to a signifcant decrease in antibiotic antibiotics, highlight promising research results and novel use in the farmed salmon industry [14, 15]. Similarly, technologies, assess challenges associated with their com‑ research has demonstrated that vaccination against Law- mercialization and use, and provide actionable strategies to sonia intracellularis, the causative agent of ileitis, in Dan‑ support their development, the United States Department of ish pig herds can reduce oxytetracycline consumption for Agriculture (USDA), with support from the World Organi‑ this condition by almost 80%; vaccination also led to sig‑ sation for Animal Health (OIE), organized the second Inter‑ nifcantly fewer pigs being treated with oxytetracycline, national Symposium on Alternatives to Antibiotics [8]. Te and improved productivity parameters such as aver‑ symposium focused on six key areas: vaccines; microbial‑ age daily gains and carcass weights [16]. Improvements derived products; non‑nutritive phytochemicals; immune‑ in mortality rates, feed conversion ratio, pig uniform‑ related products; chemicals, enzymes, and innovative drugs; ity, the occurrence of clinical diarrhea, and the need for and regulatory pathways to enable the licensure and develop‑ antibiotic treatment after L. intracellularis vaccination ment of alternatives to antibiotics [9]. Tis two‑part manu‑ have also been reported, albeit the efects were in some script synthesizes and expands on the scientifc presentations cases relatively modest and statistical signifcance was and expert panel discussions from the symposium regard‑ not assessed in all of the studies [17–19]. Notably, in one ing the use of vaccines as alternatives to antibiotics that can study on 64 farms in 9 European countries, the majority reduce the need for antibiotic use in animals. Part 1 synthe‑ of pig operations experienced cost reductions for antibi‑ sizes and expands on the expert panel discussions regarding otic treatments after L. intracellularis vaccination, even the opportunities, challenges and needs related to vaccines though not all farms were able to reduce their antibiotic that may reduce the requirement for use of antibiotics in ani‑ use [18]. mals, while part two focuses on highlighting new approaches In a study in Austrian pig herds, vaccination against and potential solutions. Other important factors relevant porcine circovirus type 2 (PCV‑2), a viral infection which to the efective use of vaccines as alternatives to antibiotics, leads to generalized immune suppression and therefore such as educational needs for producers and veterinarians, predisposes animals to secondary bacterial infections, the combination of vaccination strategies with best manage‑ led to a statistically signifcant decrease in antimicrobial ment and husbandry practices, or behavioral aspects related consumption at the farm level, even though the impact to the adoption of vaccination practices are outside the scope varied signifcantly among farm types; while the impact of this manuscript and therefore not discussed here. on fnishing farms was statistically signifcant the decline was negligible on farrow‑to‑fnish farms [20]. Te intro‑ 2 Vaccines as alternatives to antibiotics duction of PCV‑2 vaccination on a Dutch 460 sow farm Vaccines are promising alternatives to antibiotics.1 In a resulted in improvements in average daily gain, mortality recent multi‑country expert‑ranking of alternatives to the rates and decreased antibiotic use (measured as defned use of antimicrobial agents in pig production, vaccines daily doses), assessed based on data spanning 8 months before vaccination, a 4 month transition period, and 1 Alternatives to antibiotics, in this context, are new options and alternative 12 months of routine vaccination [21]. Similarly, intro‑ strategies for the prevention and treatment