Rough vaccines in animal brucellosis: Structural and genetic basis and present status

Abstract

-Brucellosis control and eradication requires serological tests and vaccines. Effective classical vaccines (S19 in cattle and Rev 1 in small ruminants), however, induce antibodies to the O-polysaccharide of the lipopolysaccharide which may be difficult to distinguish from those resulting from infection and may thus complicate diagnosis. Rough attenuated mutants lack the O-polysaccharide and would solve this problem if eliciting protective immunity; the empirically obtained rough mutants 45/20 and RB51 have been used as vaccines. Strain 45/20 is reportedly unstable and it is not presently used. RB51 is increasingly used instead of S19 in some countries but it is rifampicin resistant and its effectiveness is controversial. Some controlled experiments have found good or absolute protection in adult cattle vaccinated orally (full dose) or subcutaneously (reduced dose) and in one field experiment, RB51 was reported to afford absolute protection to calves and to perform better than S19. Controlled experiments in calves, however, have shown reduced doses of RB51 to be ineffective, full doses only partially effective, and RB51 less effective than S19 against severe challenges. Moreover, other observations suggest that RB51 is ineffective when prevalence is high. RB51 is not useful in sheep and evidence in goats is preliminary and contradictory. Rough mutants obtained by molecular biology methods on the knowledge of the genetics and structure of Brucella lipopolysaccharide may offer alternatives. The B. abortus manB core (rfbK) mutant seems promising in cattle, and analyses in mice suggest that mutations affecting only the O-polysaccharide result in better vaccines than those affecting both core and O-polysaccharide. Possible uses of rough vaccines also include boosting immunity by revaccination but solid evidence on its effectiveness, safety and practicality is not available.

From the discovery of the Malta fever?s agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosis

“…Under these conditions, the risk of disease spread from elk to elk and from elk to man (through skin wounds or by accidentally ingesting the bacteria after cleaning elk) is increased [60]. It is also worthy to note that to date, there is no vaccine that has proven to be safe and to provide a significative degree of protection in elk and bison, as well as in other wildlife species [39,54,65].…”

Isolation of Brucella pinnipedialis from Grey Seals (Halichoerus grypus) in the Baltic Sea

“…However there is a disagreement over the protective performance of strain RB51 compared with strain S19 in cattle (Moriyón et al, 2004). Each country uses slightly different methods to apply this vaccine.…”

“…In the USA, plate counts of viable organisms have been approved and used as a measure of potency (this approach is identical to the potency test for S19 vaccine in the USA (USDA, 2003). Rough vaccines for brucellosis have been discussed in some detail (Moriyón et al, 2004).…”

“…However, the presence of common core epitopes in both smooth and rough Brucella does not allow always the antibody response to RB51 to be distinguished from that induced by field smooth Brucella strains, no matter which S-LPS or OPS-based ELISA is used. The efficacy of RB51 against Brucella infection in cattle is controversial (Moriyón et al, 2004), but it is claimed that it protects against moderate challenge with virulent B. abortus, although the precise duration of this protection is unknown. The efficacy of this vaccine against B. melitensis infection in cattle is also unknown.…”

A DNA vaccine encoding p39 and sp41 of Brucella melitensis induces protective immunity in BALB/c mice

“…The development of new generation vaccine systems to prevent brucellosis is nee-ded to overcome the disadvantages of the currently used live vaccines; such as, causing abortion in pregnant animals, pathogenicity for humans, and inducing antibodies that interfere with the diagnosis of vaccinated animals (Jacques et al 2007, Grilló et al 2009. B. melitensis Rev.1 vaccine is currently the best vaccine for caprine and ovine brucellosis (Blasco 2010), despite it induces anti-LPS responses making it difficult to distinguish vaccinated from infected animals (Moriyón et al 2004). Thus, the development of a subunit vaccine free of B. melitensis LPS would have significant benefits (Ficht et al 2009).…”