Schurig Gerhardt G, Sriranganathan Nammalwar, Corbel Michael J
Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.
Vet Microbiol. 2002 Dec 20;90(1-4):479-96. doi: 10.1016/s0378-1135(02)00255-9.
The first effective Brucella vaccine was based on live Brucella abortus strain 19, a laboratory-derived strain attenuated by an unknown process during subculture. This induces reasonable protection against B. abortus, but at the expense of persistent serological responses. A similar problem occurs with the B. melitensis Rev.1 strain that is still the most effective vaccine against caprine and ovine brucellosis. Vaccines based on killed cells of virulent strains administered with adjuvant induced significant protection but also unacceptable levels of antibodies interfering with diagnostic tests. Attempts were made to circumvent this problem by using a live rough strain B. abortus 45/20, but this reverted to virulence in vivo. Use of killed cells of this strain in adjuvant met with moderate success but batch to batch variation in reactogenicity and agglutinogenicity limited application. This problem has been overcome by the development of the rifampicin-resistant mutant B. abortus RB51 strain. This strain has proved safe and effective in the field against bovine brucellosis and exhibits negligible interference with diagnostic serology. Attempts are being made to develop defined rough mutant vaccine strains that would be more effective against B. melitensis and B. suis. Various studies have examined cell-free native and recombinant proteins as candidate protective antigens, with or without adjuvants. Limited success has been obtained with these or with DNA vaccines encoding known protective antigens in experimental models and further work is indicated.
第一种有效的布鲁氏菌疫苗是基于布鲁氏菌流产株19，这是一种实验室衍生菌株，在传代培养过程中通过未知过程减毒。它能诱导对流产布鲁氏菌的合理保护，但代价是产生持续的血清学反应。对于仍然是预防山羊和绵羊布鲁氏菌病最有效疫苗的马尔他布鲁氏菌Rev.1菌株，也出现了类似问题。基于用佐剂给药的强毒株死菌细胞的疫苗诱导了显著的保护作用，但也产生了干扰诊断测试的不可接受水平的抗体。人们试图通过使用活的粗糙菌株布鲁氏菌流产株45/20来规避这个问题，但该菌株在体内恢复了毒力。在佐剂中使用该菌株的死菌细胞取得了一定成功，但反应原性和凝集原性的批次间差异限制了其应用。利福平抗性突变株布鲁氏菌流产株RB51的开发克服了这个问题。该菌株已在现场证明对牛布鲁氏菌病安全有效，并且对诊断血清学的干扰可忽略不计。人们正在尝试开发明确的粗糙突变疫苗株，这些疫苗株对马尔他布鲁氏菌和猪布鲁氏菌更有效。各种研究已经研究了无细胞天然和重组蛋白作为候选保护性抗原，无论是否使用佐剂。在实验模型中，这些疫苗或编码已知保护性抗原的DNA疫苗取得了有限的成功，表明需要进一步开展工作。
