BB0405 is a surface exposed Borrelia burgdorferi protein and its vaccination protected mice against B. burgdorferi infection. As BB0405 is highly conserved across different B. burgdorferi sensu lato species, we investigated whether vaccination with recombinant BB0405 or through intradermal bb0405 DNA tattoo vaccination could provide protection against different Borrelia species, specifically against Borrelia afzelii, the predominant B. burgdorferi sensu lato genospecies causing Lyme borreliosis across Eurasia. We immunized C3H/HeN mice with recombinant BB0405 or with a codon-optimized bb0405 DNA vaccine using the pVAC plasmid and immunized corresponding control groups mice with only adjuvant or empty vectors. We subsequently subjected these immunized mice to a tick challenge with B. afzelii CB43-infected Ixodes ricinus nymphs. Upon vaccination, recombinant BB0405 induced a high total IgG response, but bb0405 DNA vaccination did not elicit antibody responses. Both vaccine formulations did not provide protection against Borrelia afzelii strain CB43 after tick challenge. In an attempt to understand the lack of protection of the recombinant vaccine, we determined expression of BB0405 and showed that B. afzelii CB43 spirochetes significantly and drastically downregulate the expression of BB0405 protein at 37 °C compared to 33 °C, where as in B. burgdorferi B31 spirochetes expression levels remain unaltered. Vaccination with recombinant BB0405 was previously shown to protect against B. burgdorferi sensu stricto. Here we show that vaccination with either recombinant BB0405 (or non-immunogenic bb0405 DNA), despite being highly conserved among B. burgdorferi sl genospecies, does not provide cross-protection against B. afzelii, mostly likely due to downregulation of this protein in B. afzelii in the mammalian host.

BB0405 是一种表面暴露的伯氏疏螺旋体蛋白，其疫苗接种保护小鼠免受伯氏疏螺旋体感染。由于 BB0405 在不同的B. burgdorferi sensu lato 物种中高度保守，我们研究了重组 BB0405 疫苗接种或通过皮内bb0405 DNA 纹身疫苗接种是否可以提供针对不同疏螺旋体物种的保护，特别是针对引起主要的B. burgdorferi sensu lato 基因种的Borrelia afzelii横跨欧亚大陆的莱姆疏螺旋体病。我们用重组 BB0405 或密码子优化的bb0405免疫 C3H/HeN 小鼠DNA疫苗使用pVAC质粒，仅用佐剂或空载体免疫相应对照组小鼠。我们随后让这些免疫小鼠接受了B. afzelii CB43 感染的蓖麻若虫的蜱攻击。接种疫苗后，重组 BB0405 诱导高总 IgG 反应，但bb0405 DNA 接种未引发抗体反应。两种疫苗制剂在蜱攻击后均不提供针对伯氏疏螺旋体菌株 CB43 的保护。为了了解重组疫苗缺乏保护，我们确定了 BB0405 的表达并表明B. afzelii与 33 °C 相比，CB43 螺旋体在 37 °C 下显着且大幅下调 BB0405 蛋白的表达，而在B. burgdorferi B31 螺旋体中， B31 螺旋体的表达水平保持不变。先前已证明用重组 BB0405 接种疫苗可预防严格意义上的伯氏疏螺旋体。在这里我们用重组BB0405（或无免疫原性疫苗接种bb0405 DNA），尽管中被高度保守的伯氏疏螺旋SL基因种，不提供交叉保护，防止B. afzelii，最有可能是由于这种蛋白的下调乙.哺乳动物宿主中的afzelii。