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The Advances in Brucellosis Vaccines

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The Advances in Brucellosis Vaccines Vaccine 37 (2019) 3981–3988 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Review The advances in brucellosis vaccines ⇑ Huanhuan Hou a,1, Xiaofeng Liu b,1, Qisheng Peng a, a Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China b Tumor Hospital of Jilin Province, Changchun 130021, China article info abstract Article history: Brucellosis is a worldwide zoonosis affecting animal and human health. Till now, there is no effective vac- Received 12 November 2018 cine licensed for brucellosis in humans. Although M5, H38 and 45/20 vaccines were used to prevent ani- Received in revised form 4 May 2019 mal brucellosis in the early stages, the currently used animal vaccines are S19, Rev.1, S2, RB51 and SR82. Accepted 21 May 2019 However, these vaccines still have several drawbacks such as residual virulence and interfering conven- Available online 5 June 2019 tional serological tests. With the development of DNA recombination technologies and the completion of the sequence of Brucella genome, much research focuses on the search for potential safer and more effec- Keywords: tive vaccines. Preliminary studies have demonstrated that new vaccines, including genetically engineered Brucellosis attenuated vaccines, subunit vaccines and other potential vaccines, have higher levels of protection, but Vaccine there are still some problems. In this paper, we briefly review the main vaccines that have been used in controlling the brucellosis for decades and the progress in the development of new brucellosis vaccines. Ó 2019 Elsevier Ltd. All rights reserved. Contents Introduction . ..................................................................................................... 3982 1. Common smooth vaccines . .................................................................................. 3982 1.1. Brucella abortus vaccine strain S19. ........................................................................ 3982 1.2. B. melitensis Rev.1 vaccine . ........................................................................ 3982 1.3. B. melitensis H38 vaccine ........................................................................................ 3982 1.4. B. melitensis M5 vaccine . ........................................................................................ 3983 1.5. B. suis vaccine strain S2 . ........................................................................................ 3983 2. Common rough vaccines . .................................................................................. 3983 2.1. B. abortus RB51 vaccine. ........................................................................................ 3983 2.2. B. abortus 45/20 vaccine . ........................................................................................ 3983 2.3. B. abortus SR82 vaccine. ........................................................................................ 3983 3. Genetically engineered attenuated vaccines. ............................................................... 3983 4. Vector-delivered Brucella vaccines . .................................................................................. 3984 5. Subunit vaccines..................................................................................................... 3984 5.1. Recombinant protein. ........................................................................................ 3984 5.2. DNA vaccine. ........................................................................................ 3984 5.3. Synthetic peptide vaccines . ........................................................................ 3985 6. Other potential vaccines . .................................................................................. 3985 6.1. Brucella ghost vaccine . ........................................................................................ 3985 6.2. Nanoparticle vaccine . ........................................................................................ 3985 6.3. Vaccine candidates identified via a reverse vaccinology approach . ..................................................... 3985 7. Vaccines in clinical trials . .................................................................................. 3985 8. Conclusions and prospective . .................................................................................. 3986 Declaration of Competing Interest . .................................................................................. 3986 ⇑ Corresponding author. E-mail address: [email protected] (Q. Peng). 1 Both authors contributed equally to this work. https://doi.org/10.1016/j.vaccine.2019.05.084 0264-410X/Ó 2019 Elsevier Ltd. All rights reserved. 3982 H. Hou et al. / Vaccine 37 (2019) 3981–3988 Acknowledgments . ........................................................................................ 3986 References . ........................................................................................................ 3986 Introduction United States demonstrated that 65% of immunized with S19 were not infected with Brucella again, and clinical symptoms such as mis- Brucellosis is a zoonotic disease caused by Brucella, which carriage were improved obviously in another 35% of immunized spreads in more than 170 countries and regions around the world animals [17]. S19 is the smooth Brucella strain phenotype, and its [1]. Brucellosis in human is characterized by a chronic debilitating LPS still contains O-polysaccharide that can continuously stimulate disease including nonspecific influenza-like symptoms, diaphore- animal to produce anti-LPS antibodies, which interferes with con- sis, and bacteremia among others [2]. Since the late 1980s, the epi- ventional serological tests between immunized and naturally demic of brucellosis in some countries and regions are rapidly infected animals. For the improvement of S19 vaccine and maintain escalating, it infects more than 60 species of wild animals, forms its good immunogenicity and genetic stability, it is possible to a worldwide endemic disease and causes large economic losses improve the efficiency and ease of differential diagnosis by adding in animal husbandry [3]. Preventing and treating this disease is marker genes. At present, multiple candidates can be used as mar- imperative, but it has a long way to go. For animals with high eco- ker genes, such as bp26 and P39 gene. Experiments showed that the nomic value and losses after infection, developing countries are not absence of Bp26 or P39 protein does not affect the protection of S19 suitable for brucellosis eradication programs [4–6]. vaccine in mouse or pregnant cows [18,19]. Although S19 is an offi- Since the beginning of the twentieth century, the research work cially approved vaccine, which is widely used to prevent brucellosis on the development of vaccines for brucellosis started [7]. The worldwide, S19 vaccine can still cause orchitis in adult males, pro- development of brucellosis vaccines has experienced inactivated longed infection, and gravid females may miscarry [20]. Moreover, vaccines, live attenuated vaccines, and rough attenuated vaccines. S19 has a certain degree of virulence to humans [21]. In recent Inactivated vaccines were used in the early stages for the preven- years, there have been many human brucellosis reported cases tion and control of brucellosis, and have subsequently been caused by vaccine production or vaccination around the world replaced by attenuated live vaccines which are more immune- [22,23]. In addition, there is little understanding of immune effective [8]. The attenuated live vaccines currently used include response induced by S19 vaccination in large animals. Definition S19, Rev.1, S2, SR82 and RB51 [9,10]. RB51 is the only officially of immune markers correlated protection will be helpful in the approved rough attenuated vaccine. These vaccines are widely screening of more effective S19. In the future, the recombinant used but still have some drawbacks. For example, some of these DNA technologies should be utilized to develop a better S19 in vaccines can cause human infection and possible abortion compli- terms of safety, efficacy and other desirable characteristics. cations in pregnant female cattle [11]. Although the existing vacci- nes have some deficiencies, they have played an essential role in 1.2. B. melitensis Rev.1 vaccine prevention of brucellosis worldwide. With the development of molecular biology techniques and the deep understanding of The Rev.1 vaccine is a type of streptomycin-resistant smooth B. pathogenic mechanism of Brucella, new genetic engineering vacci- melitensis strain [24]. The formulation of Rev.1 vaccine is whole nes are expected to replace traditional vaccines for brucellosis con- organism of the live attenuated B. melitensis strain derived from a trol [12]. In this study, we briefly review the main vaccines that virulent B. melitensis isolate. Adjuvants are not used in Rev.1 vac- have been used in controlling the brucellosis for decades and the cine. This vaccine was used to prevent animal brucellosis in the advance in new brucellosis vaccines. 1960s in many countries such as Greece, Jordan, Tajikistan, Mongo- lia and Spain [25]. In 1990s, Rev.1 vaccine was introduced into 1. Common smooth vaccines China to prevent and control the infection with B. ovis [14]. Rev.1 vaccine is innocuous when administered to rams [26]. Rev.1 also 1.1. Brucella abortus vaccine strain S19 seems
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