Oliveira Aline F, Ferraz Luciana C, Brocchi Marcelo, Roque-Barreira Maria-Cristina
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil.
Microbes Infect. 2007 Mar;9(3):382-90. doi: 10.1016/j.micinf.2006.12.019. Epub 2007 Jan 12.
Rhodococcus equi remains one of the most important pathogens of foals and vaccination strategies to prevent rhodococcosis are under increasing investigation. Attenuated Salmonella strains carrying heterologous antigens offer an advantageous alternative to conventional vaccines, especially because they induce mucosal and systemic immunity. In this work, we expressed the VapA antigen from R. equi in a Salmonella enterica Typhimurium strain, which was able to colonize and persist in the lymphoid tissue of BALB/c mice. Two days after being challenged, oral immunized mice presented a 3- to 7-fold increase in R. equi clearance. This was progressively enhanced during infection and, on the 10th day, a CFU value 50-fold lower than that recovered from non-immunized mice was attained. The number of hepatic granulomas was 2 times lower, and leukocyte infiltration was transiently detected in immunized mice, contrasting with the severe inflammation and necrosis presented by non-immunized mice. Infection with 1 x 10(7)R. equi CFU caused 100% mortality in the control groups, while all immunized mice survived. This protection was associated with the detection of high levels of anti-VapA IgG in the serum of the vaccinated mice, predominantly the IgG2a isotype. Our results suggest that attenuated Salmonella encoding VapA may be used in foals to prevent rhodococcosis.
马红球菌仍然是幼驹最重要的病原体之一,预防马红球菌病的疫苗接种策略正在受到越来越多的研究。携带异源抗原的减毒沙门氏菌菌株为传统疫苗提供了一种有利的替代方案,特别是因为它们能诱导黏膜和全身免疫。在这项研究中,我们在鼠伤寒沙门氏菌菌株中表达了来自马红球菌的VapA抗原,该菌株能够在BALB/c小鼠的淋巴组织中定殖并持续存在。在受到攻击两天后,经口服免疫的小鼠对马红球菌的清除能力提高了3至7倍。在感染过程中,这种清除能力逐渐增强,在第10天时,获得的菌落形成单位(CFU)值比未免疫小鼠低50倍。免疫小鼠的肝脏肉芽肿数量减少了一半,并且短暂检测到白细胞浸润,这与未免疫小鼠出现的严重炎症和坏死形成对比。用1×10⁷CFU的马红球菌感染导致对照组100%死亡,而所有免疫小鼠均存活。这种保护作用与在接种疫苗小鼠血清中检测到高水平的抗VapA IgG有关,主要是IgG2a亚型。我们的结果表明,编码VapA的减毒沙门氏菌可用于幼驹预防马红球菌病。