title: Meta-Analysis and Advancement of Brucellosis Vaccinology.
abstract: OBJECTIVE
  In spite of all the research effort for developing new vaccines against brucellosis, it remains unclear whether these new vaccine technologies will in fact become widely used. The goal of this study was to perform a meta-analysis to identify parameters that influence vaccine efficacy as well as a descriptive analysis on how the field of Brucella vaccinology is advancing concerning type of vaccine, improvement of protection on animal models over time, and factors that may affect protection in the mouse model.
  
  
  METHODS
  A total of 117 publications that met the criteria were selected for inclusion in this study, with a total of 782 individual experiments analyzed.
  
  
  RESULTS
  Attenuated (n = 221), inactivated (n = 66) and mutant (n = 102) vaccines provided median protection index above 2, whereas subunit (n = 287), DNA (n = 68), and vectored (n = 38) vaccines provided protection indexes lower than 2. When all categories of experimental vaccines are analyzed together, the trend line clearly demonstrates that there was no improvement of the protection indexes over the past 30 years, with a low negative and non significant linear coefficient. A meta-regression model was developed including all vaccine categories (attenuated, DNA, inactivated, mutant, subunit, and vectored) considering the protection index as a dependent variable and the other parameters (mouse strain, route of vaccination, number of vaccinations, use of adjuvant, challenge Brucella species) as independent variables. Some of these variables influenced the expected protection index of experimental vaccines against Brucella spp. in the mouse model.
  
  
  CONCLUSIONS
  In spite of the large number of publication over the past 30 years, our results indicate that there is not clear trend to improve the protective potential of these experimental vaccines.
authors.affiliation: Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Tatiane F
authors.initials: TF
authors.lastname: Carvalho
authors.affiliation: Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: João Paulo A
authors.initials: JP
authors.lastname: Haddad
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Tatiane A
authors.initials: TA
authors.lastname: Paixão
authors.affiliation: Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Renato L
authors.identifier: http://orcid.org/0000-0002-4830-0470
authors.initials: RL
authors.lastname: Santos
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D002004:Brucella Vaccine / Q000276:immunology / Q000627:therapeutic use*; D002003:Brucella abortus / Q000276:immunology / Q000472:pathogenicity; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D002004:Brucella Vaccine; D014613:Vaccines, Attenuated