STATEMENT REGARDING SEQUENCE LISTING

The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is SEQUENCE_LISTING_210260_401USPC.txt. The text file is 2.84 KB, was created on May 22, 2020, and is being submitted electronically via EFS-Web.

BACKGROUND

Technical Field

The present invention can be included in the field of new therapeutics for the treatment and/or prevention of brucellosis. Specifically, the present application relates to a new vaccine strain of the genusBrucella. The strain can be used as a medicament, specifically for the treatment and/or prevention of brucellosis.

Description of the Related Art

Brucellosis is a zoonotic disease. In animals,Brucellainfection causes abortions, infertility, decreased production and limitations to the trading of animals and animal products. In addition, the bacteria are transmitted from infected animals to humans, thereby inflicting a debilitating and often disabling disease, against which there is no vaccine and whose treatment requires high doses of antibiotics for prolonged periods with frequent relapses.

Therefore, brucellosis is a significant public health problem. It has been shown that the prevalence of human brucellosis is directly related to the prevalence of animal brucellosis. Thus, and in the absence of vaccines for use in humans, prevention of the disease requires the control of the infection in animals. In most socio-economic contexts, the only feasible way to control brucellosis is through programs based on the vaccination of farm animals, either through mass vaccination programs or through programs for the vaccination, diagnosis and slaughter of infected animals.

The reference vaccines against animal brucellosis are the smooth (S) strainsBrucella abortusS19 for cattle andBrucella melitensisRev1 for sheep and goats (OIE Terrestrial Manual, 2016—chapters 2.4.3. and 2.7.2). Both are live attenuated vaccines, adjuvant-free, with a low cost of production and acquisition, and highly effective against infection by field strains in ruminants (main source of infection for humans). However, a technical drawback is that they generate an immune response after vaccination indistinguishable from that induced after virulent infection by field strains, generating a problem for differentiating between infected and vaccinated animals (DIVA). To solve this problem, numerous scientific efforts have been made. One strategy has consisted in the development of rough (R) strains ofBrucella, which, due to the absence of the O-Polysaccharide (O-PS) of lipopolysaccharide (LPS)—a known virulence factor ofBrucellaand the main antigen used in tests for serological diagnosis of infection—has led to attenuated strains usable as live vaccines, which do not significantly interfere in the serological diagnostic tests. In this context, in the 90's, the spontaneous mutant with an R phenotype known asB. abortusRB51 was developed by subculturing (Schurig et al., 1991. Veterinary Microbiology, 28: 171-188). Strain RB51 has been used in some countries against bovine brucellosis, with controversial results. Both RB51 and a collection of R mutants derived fromB. melitensisgenetically well characterized in the different LPS synthesis pathways (Godfroid et al., 2000. Res Microbiol, 151: 655-668; Gonzalez et al., 2008. PLoS One, 3(7): e2760), reduce interference problems in the serological diagnosis of virulent infection, due to the absence of O-PS antigen. However, it has been shown that R vaccines are not ideal, because the protection they confer against virulent infections is well below that of the reference vaccinesB. abortusS19 andB. melitensisRev1 (Gonzalez et al., 2008. PLoS One, 3(7): e2760; Barrio et al., 2009. Vaccine, 27: 1741-1749).

On the other hand, bacterial tagging with the xenogenic protein Green Fluorescent Protein (GFP) has been proposed to solve the DIVA problem (Chacón-Diaz et al., 2011. Vaccine. 29(3): 577-82).

Moreover, current vaccines also have other issues such as to induce abortions and to be present in the milk of adult animals previously vaccinated (OIE Terrestrial Manual, 2016—chapters 2.4.3. and 2.7.2), to generate human infections and, in the case ofB. melitensisRev1, to be resistant to streptomycin (antibiotic of choice). Therefore, there is currently a need for an effective brucellosis vaccine and/or therapeutic which does not have all of the aforementioned drawbacks.

It is an objective of the present invention to provide a superiorBrucellastrain for the treatment and/or prevention of brucellosis.

