Chang Y F, Appel M J, Jacobson R H, Shin S J, Harpending P, Straubinger R, Patrican L A, Mohammed H, Summers B A
Diagnostic Laboratory, James A. Baker Institute for Animal Health, Cornell University, Ithaca, New York 14853, USA.
Infect Immun. 1995 Sep;63(9):3543-9. doi: 10.1128/iai.63.9.3543-3549.1995.
Twenty-two specific-pathogen-free beagles were vaccinated with recombinant OspA (ospA gene derived from Borrelia burgdorferi B31) alone or with adjuvant (QuilA, Montanide ISA25, or aluminum hydroxide) at 6 weeks of age. Thirteen dogs were used as nonvaccinated controls with or without adjuvant. Three dogs were kept as contact controls and received neither vaccine nor challenge. Six weeks or 6 months after the first vaccination, the vaccinated (20 of 22) and nonvaccinated dogs (13) were challenged by exposure to adult ticks (Ixodes scapularis) naturally that were infected with B. burgdorferi (tick infection rate, > or = 60%) and that were collected from Westchester County, N.Y. Protection from infection was evaluated by culture for B. burgdorferi from skin biopsies taken near the sites of tick bites. Skin biopsies were taken at monthly intervals for 3 months. B. burgdorferi was not isolated from any of the vaccinated dogs. In contrast, 12 of 13 control dogs challenged by exposure to the ticks were culture positive. The histopathology of the joint capsules 3 months after the challenge was used to evaluate protection from arthritis. Eight of 13 control dogs showed synovitis in single or multiple joints, while only 1 of the 22 vaccinated dogs had a single focus of mild inflammation in a single joint. At the time of the challenge, the vaccinated dogs had antibody to B. burgdorferi, which was demonstrable by kinetic enzyme-linked immunosorbent assay, Western blotting (immunoblotting), and a serum growth inhibition assay. The vaccinal antibody declined gradually after the challenge, especially in dogs vaccinated with OspA without adjuvants. Antibodies in the challenge control dogs were only detectable by 4 to 6 weeks after the challenge and remained at high levels until the termination of the study. Contact control dogs showed no antibody responses or histopathologic lesions and were culture negative. By Western blot analysis, antibodies to OspA first appeared in the sera of vaccinated dogs 3 weeks after the first vaccination. The absence of additional bands after the challenge suggests that infection in vaccinated dogs was blocked. Results from this study show that vaccination with recombinant OspA protected dogs against infection and disease after an experimental challenge with B. burgdorferi by exposure to ticks.
22只无特定病原体的比格犬在6周龄时单独接种重组OspA（源自伯氏疏螺旋体B31的ospA基因）或与佐剂（QuilA、Montanide ISA25或氢氧化铝）联合接种。13只犬用作未接种疫苗的对照，有或无佐剂。3只犬作为接触对照，既不接种疫苗也不接受攻毒。首次接种后6周或6个月，接种疫苗的犬（22只中的20只）和未接种疫苗的犬（13只）通过暴露于自然感染伯氏疏螺旋体的成年肩突硬蜱（蜱感染率≥60%，从纽约州韦斯特切斯特县采集）进行攻毒。通过对蜱叮咬部位附近皮肤活检组织进行伯氏疏螺旋体培养来评估感染防护情况。在3个月内每月进行一次皮肤活检。未从任何接种疫苗的犬中分离出伯氏疏螺旋体。相比之下，13只接受蜱暴露攻毒的对照犬中有12只培养呈阳性。攻毒3个月后关节囊的组织病理学用于评估关节炎防护情况。13只对照犬中有8只在单个或多个关节出现滑膜炎，而22只接种疫苗的犬中只有1只在单个关节有单个轻度炎症病灶。在攻毒时，接种疫苗的犬具有针对伯氏疏螺旋体的抗体，可通过动力学酶联免疫吸附测定、蛋白质印迹法（免疫印迹）和血清生长抑制测定检测到。攻毒后疫苗抗体逐渐下降，尤其是未加佐剂接种OspA的犬。攻毒对照犬中的抗体在攻毒后4至6周才可检测到，并在研究结束前一直保持高水平。接触对照犬未显示抗体反应或组织病理学病变，培养呈阴性。通过蛋白质印迹分析，接种疫苗的犬在首次接种后3周血清中首次出现针对OspA的抗体。攻毒后未出现额外条带表明接种疫苗的犬中的感染被阻断。本研究结果表明，接种重组OspA可使犬在经暴露于蜱进行伯氏疏螺旋体实验性攻毒后免受感染和疾病。
