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Frontiers in Biology

Front Biol    2013, Vol. 8 Issue (1) : 60-77
Progress in Brucella vaccine development
Xinghong YANG(), Jerod A. SKYBERG, Ling CAO, Beata CLAPP, Theresa THORNBURG, David W. PASCUAL
Department of Immunology & Infectious Diseases, Montana State University, Bozeman, MT 59717-3610, USA
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Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines.

Keywords Brucella      brucellosis      zoonosis      livestock vaccines     
Corresponding Author(s): YANG Xinghong,   
Issue Date: 01 February 2013
 Cite this article:   
Xinghong YANG,Jerod A. SKYBERG,Beata CLAPP, et al. Progress in Brucella vaccine development[J]. Front Biol, 2013, 8(1): 60-77.
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Ling CAO
Fig.1  The transmission chain of spp. among wildlife, livestock, and human. Livestock acquires the diseases from the natural reservoirs, such as bison, elk, and deer. Subsequently, humans are infected by the sick livestock and/or its products, either via inhalation of contaminated aerosol, ingestion of foods such as unpasteurized milk and cheese, or direct contact with the sick livestock and its contaminated products.
Live vaccine strainsAnimalsImmunization dose/route1Challenge strain2 /dose/route1Efficacy3 (protection against abortion)References
B. abortus
S19heifers109-1010/s.c.2308/9×106/i.c.70%-91%(Confer et al., 1985)
heifers109-1010/s.c.2308/5×107/i.c.0%-20%(Confer et al., 1985)
heifers107 (x2)/s.c.2308/9×105/i.c.86%(Wyckoff et al., 2005)
heifers1.0-1.4x1010/s.c.2308/1×107/ i.c.100%(Cheville et al., 1996b)
bison5x108/s.c.2308/1×107/i.c.67%(Davis et al., 1991)
RB51heifers1.0-1.4×1010/s.c.2308/1×107/ i.c.100%(Cheville et al., 1996b)
heifers1.0-1.4×1010/s.c.2308/1×107/i.c.100%(Cheville et al., 1993)
cattle5x109/s.c.field spp.100%(Lord et al., 1998)
cows1.5-1.6×1010/s.c.2308/3×107/i.c.75%(Poester et al., 2006)
elk108-109/i.m.,bb2308/1×107/i.c.12%-25%(Cook et al., 2002)
elk1010 /i.m.2308/1×107/i.c.0%(Kreeger et al., 2002)
elk1010 (x2)/i.m.2308/1×107/i.c.7%(Kreeger et al., 2002)
(lg units)
Δpgk Δpgm ΔznuA 2308BALB/c mice105/i.p.2308/1×106/i.p.0.96(Trant et al., 2010)
C57BL/6 mice105/i.p.2308/1×106/i.p.1.36(Trant et al., 2010)
129/Sv mice105/i.p.2308/1×106/i.p.3.28(Trant et al., 2010)
BALB/c mice107/i.p.2308/5×105/i.p.1.9-2.3(Ugalde et al., 2003)
BALB/c mice108/i.p.2308/5×104/i.p.1.88(Yang et al., 2006)
(protection against abortion)
B. melitensis
Rev-1goats1.5×109/(uk)640/4×1010/i.m.100%(Alton, 1966)
sheep2×109/s.c.Isfahan/6×109/s.c.100%(Entessar et al., 1967)
goats1.5×109/(uk)field spp.100%(Alton, 1968)
(lg units)
RBM17BALB/c mice108/i.p.16M/2×105/i.p.2.83(Adone et al., 2005)
Bm16MRwaBALB/c mice108/i.p.H38/1×104/i.p.3.9-4.4(González et al., 2008)
Bm16MRwzmBALB/c mice108/s.c.H38/1×104/i.p.4.1(González et al., 2008)
ΔznuA 16MBALB/c mice3x1011/oral16M/2×104/i.n.3.0-4(Clapp et al., 2011a)
IFN-γ-/- mice3x1011/oral16M/2×104/i.n.1.85(Clapp et al., 2011a)
RWP5goats109/s.c.16M/1×107/i.c.100%(Phillips et al., 1997)
Δomp25 16Mgoats109/s.c.16M/1×107/i.c.100%(Edmonds et al., 2002b)
16MΔmucRBALB/c mice106/i.p.16M/6×105/i.p.2.79(Arenas-Gamboa et al., 2011)
16MΔvjbRBALB/c mice106/i.p.16M/1×105/i.p.~2.4(Wang et al., 2011)
vjbR::Tn5 16MBALB/c mice105/i.p.16M/1×105/i.p.4.98(Arenas-Gamboa et al., 2008)
(protection against abortion)
B. suis
S2sheep0.2-5×1010/oralB. melitensis 28/107/i.c. or 109/oral82.7%(Xin, 1986)
goats0.25-5×1010/oralB. melitensis 28/107/i.c. or 109/oral82.1%(Xin, 1986)
sows2×1010 (×2)/oralB.suis 12/6x107/oral75.0%(Xin, 1986)
cows0.25-5×1010/oralB.abortus 387/106-107/i.c.71.4%(Xin, 1986)
Tab.1  Live vaccine immunization regimens and protective efficacies
Subunit VaccinesMice1Immunization/ formula/dose/route2Challenge strain3 /dose/routeEfficacy4 (lg)References
B. abortus
BLSBALB/cDNA/100 μg (×4)/i.m.544/105/i.p.1.25-1.65(Velikovsky et al., 2002)
InfCBALB/cprotein/5 μg (×1)/i.p.2308/1×104/i.p.1.92(Cespedes et al., 2000)
L7/L12BALB/cByJDNA/100 μg (×1)/i.m.2308/1×106/i.p.0.47-1.26(Kurar and Splitter, 1997)
Omp16BALB/cprotein/10 μg (×2)/i.p.544/4×104/i.p.1.97(Pasquevich et al., 2009)
Omp19BALB/cprotein/10 μg (×2)/i.p.544/4×104/i.p.1.85(Pasquevich et al., 2009)
Omp28Swiss Albinoprotein/30 μg (×2)/i.m.544/1×105/i.p.0.97(Kaushik et al., 2010)
P39BALB/cprotein/20 μg (×2)/i.m.544/5×104/i.p.1.21-2.48(Al-Mariri et al., 2001)
DnaKBALB/cprotein/30 μg (×2)/i.p.2308/1×104/i.p.0.90-0.95(Delpino et al., 2007)
SurABALB/cprotein/30 μg (×2)/i.p.2308/1×104/i.p.0.97-1.45(Delpino et al., 2007)
SodCBALB/cDNA/10 μg (×1)/i.s.2308/1×104/i.p.1.52(Munoz-Montesino et al., 2004)
SodCBALB/cDNA/10 μg (×1)/i.m.2308/1×104/i.p.1.15(Munoz-Montesino et al., 2004)
B. melitensis
Bp26BALB/cDNA/300 μg (×4)/i.m.16M/2.4×104/i.p.1.16(Yang et al., 2005)
Omp25BALB/cDNA/400 μg (×4)/i.m.16M/1×104/i.p.2.54(Commander et al., 2007)
IalBBALB/cDNA/400 μg (×4)/i.m.16M/1×104/i.p.2.70(Commander et al., 2007)
Omp31BALB/cDNA/100 μg (×4)/i.m.H38S/1×104/i.v.1.30-1.45(Cassataro et al., 2005)
AdoHcyaseBALB/cprotein/100 μg (×2)/i.p.16M/5×105/i.p.1.13-2.13(Yang et al., 2011)
Tab.2  Subunit vaccine immunization regimens and protective efficacies.
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