  Citation: Dudek, K.; Sevimli, U.; Migliore, S.; Jafarizadeh, A.; Loria, G.R.; Nicholas, R.A.J. Vaccines for Mycoplasma Diseases of Small Ruminants: A Neglected Area of Research. Pathogens 2022, 11, 75. https://doi.org/10.3390/ pathogens11010075 Academic Editor: Maria Filippa Addis Received: 14 November 2021 Accepted: 4 January 2022 Published: 7 January 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). pathogens Review Vaccines for Mycoplasma Diseases of Small Ruminants: A Neglected Area of Research Katarzyna Dudek 1 , Umit Sevimli 2 , Sergio Migliore 3 , Amirreza Jafarizadeh 4 , Guido R. Loria 3 and Robin A. J. Nicholas 5, * 1 Department of Cattle and Sheep Diseases, National Veterinary Research Institute, 57 Partyzantów Avenue, 24100 Pulawy, Poland; katarzyna.dudek@piwet.pulawy.pl 2 Pendik Veterinary Control Institute, OIE Reference Laboratory for CCPP, Pendik, Istanbul 34890, Turkey; umit.sevimli@outlook.com 3 Area Diagnostica Specialistica, OIE Reference Laboratory for Contagious Agalactia, Istituto Zooprofilattico Sperimentale della Sicilia, Via G. Marinuzzi 3, 90129 Palermo, Italy; sergio.migliore@izssicilia.it (S.M.); guidoruggero.loria@izssicilia.it (G.R.L.) 4 Departmentof Microbiology, Faculty of Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran 477893855, Iran; a.jafarizade@gmail.com 5 The Oaks, Nutshell Lane, Farnham, Surrey GU9 0HG, UK * Correspondence: robin.a.j.nicholas@gmail.com Abstract: Mycoplasmas cause some of the most economically important diseases of sheep and goats, including diseases listed by the World Organisation for Animal Health (OIE) such as contagious caprine pleuropneumonia (CCPP) and contagious agalactia (CA). Other important mycoplasma diseases include chronic respiratory and arthritic syndrome (CRAS) and atypical pneumonia, both present on all continents where small ruminants are farmed. Unfortunately, owing to a lack of investment, most commercial vaccines for these diseases are of poor quality, being mostly composed of killed bacteriocins of dubious or unknown efficacy. Several Mediterranean laboratories produce autogenous vaccines, but these can only be used on farms where outbreaks have been officially declared, and consequently have limited impact on disease nationally. Effective live vaccines are available, but their use is often restricted because of safety concerns. With the necessary safeguards in place, we argue for their greater use. This review examines reported vaccines for mycoplasma diseases of small ruminants and attempts to identify new candidate antigens that may enable the development of improved products. Vaccines for CCPP are covered elsewhere. Keywords: small ruminants; mycoplasma; vaccines 1. Introduction Some of the most economically important diseases of sheep and goats are caused by mycoplasmas, small wall-less bacteria of the class Mollicutes. These include diseases listed by the World Organisation for Animal Health (OIE), such as contagious caprine pleuropneumonia (CCPP) and contagious agalactia (CA), as well as chronic respiratory and arthritic syndrome (CRAS) and atypical pneumonia, both present on all continents where small ruminants are farmed (Table 1). The true impact of these diseases is hard to determine, because their prevalence is mostly unknown as laboratories carrying out mycoplasma identification are not available everywhere. Furthermore, small ruminants are mostly managed by the poorer sector of the agricultural industry where the value of individual animals is low with very small or negligible profit margins. Consequently, the development of vaccines is a risky venture for commercial companies, which require large upfront expenditure with no certainty of uptake, particularly by subsistence farmers lacking the ability to pay for them. This lack of funding for effective vaccines is reflected in the poor quality of existing products available for the main mycoplasma diseases: nearly Pathogens 2022, 11, 75. https://doi.org/10.3390/pathogens11010075 https://www.mdpi.com/journal/pathogens