Brucellosis Vaccines for the 21^st Century…. 
A Research Update

Dr. Philip H. Elzer, Louisiana State University AgCenter and School of Veterinary Medicine, Department of Veterinary Science, 111 Dalrymple Building, Baton Rouge, LA; 70803.

There are six recognized species in the genus Brucella. These Gram negative facultative intracellular pathogens are characterized by their host specificity and cause chronic infections in many ungulates and man.  Brucellae are know to cause abortion and infertility in wild and domestic ungulates.  Besides the agricultural economic loss associated with brucellosis, four species of brucellae are zoonotic agents.  After the recent tragic events associated with September 11, 2001, three species of Brucella are also considered “agents of mass destruction.”  Therefore the development of a safe and efficacious vaccine for all ungulates and humans is a future goal of brucellosis research.

Brucella abortus primarily infects cattle, bison and elk and causes abortions and infertility in the females.  The United States is currently on the verge of eradicating this disease in domestic cattle.  However, the wildlife reservoirs of infected bison and elk in the Greater Yellowstone Area are delaying this goal.  Currently B. abortus strain RB51 is the accepted commercial vaccine to control the spread of bovine brucellosis. 

Brucella suis primarily infects swine and reindeer.  In the United States, there is a swine brucellosis eradication program; but it is hampered by the large number of feral swine which carry this disease as well as pseudorabies.  Unlike B. abortus, B. suis is a venereal disease which causes infertility in both the males and females.  Typically swine brucellosis is undetected in a herd during the early stages of infection, and economic losses are due to low production in the herd. 

Brucella melitensis infects sheep and goats throughout the world. Brucella melitensis is non-venereal and causes placentitis resulting in abortion similar to B. abortus infections.  Brucella melitensis is considered the most virulent of the brucellae to man, and it is postulated that only 1-10 colony forming units are needed to infect humans.  This low infectious dose combined with the ease of aerosolizing B. melitensis would  make it an effective biological weapon.

Human brucellosis, also known as “undulant fever,” is characterized by cyclical fever that starts two to three weeks post-exposure.  Night sweats, headaches, backaches, and general malaise are symptoms associated with acute infection.  Chronic brucellosis can lead to a debilitating condition, including arthritis, dementia and even death.  The CDC classifies B. abortus, B. melitensis and B. suis as “agents of mass destruction” and as category B organisms.  Brucella canis, a less virulent strain, can cause human disease but only when contracted by an immuno-suppressed individual.  Currently there is no approved vaccine for human use, and a vast majority of the animal vaccines are virulent to man.

Worldwide there are five Brucella vaccines for use in animal populations.   These brucellosis vaccines are B. abortus 45/20, B. melitensis Rev-1, B. suis strain 2, B. abortus strain 19, and B. abortus RB51.   The killed vaccine strain 45/20 did not consistently protect against virulent challenge and also caused some abortions.  B. suis strain 2  has not be evaluated extensively and  can cause vaccinal titers which can not be distinguished from field strain titers.  Rev-1 provides protection in sheep and goats against brucellosis; however, it can cause abortions and vaccinal titers in some animals.  Strain 19 also protects cattle against brucellosis but may also cause abortions and titers which interfere with routine diagnostic test.  It is not effective in wildlife species infected with B. abortus, primarily bison and elk. 

Currently B. abortus strain RB51 is the only vaccine that does not cause vaccinal titers which can be confused with field strain titers.  RB51 is approved for use in cattle and provides equivalent levels of protection as compared to Strain 19.  RB51 appears to be safe in the majority of ungulates and non-target species tested in that it does not cause abortion.  RB51 does cause abortions in pregnant reindeer, and it is not efficacious against virulent challenge in elk and bison.  With no vaccines to protect wildlife, primarily bison, elk and swine (feral swine carry brucellosis, it is imperative that new vaccine candidates be evaluated.

Our research lab is evaluating 5 new vaccine candidates for use in wildlife and domestic animals.  We have made OMP25 gene deletion mutants in B. abortus, B. melitensis, and B. ovis.  These vaccines have been tested in cattle, goats and sheep and did not demonstrate any detrimental effects.  Vaccinal titers can be distinguished from field strain titers using these vaccine strains.  The B. melitensis mutant does not cause abortions protects goats against virulent challenge.

We have been testing a new B. suis strain VTRS-1 in swine.  VTRS-1 is a rough derivative of virulent B. suis, and vaccination of swine with this strain does not cause vaccinal titers or abortion.  VTRS-1 also provides sows protection against virulent challenge.

Future endeavors in my laboratory include the development of multivalent vaccines using RB51 as a vector to deliver antigens.  A vaccine efficacious against brucellosis and/or tuberculosis, Johne’s Disease, or pseudorabies would facilitate both domestic and wildlife disease prevention.  The characterization of safe and effective animal vaccines will assist in the development of a human brucellosis vaccine.