Warfield Kelly L, Swenson Dana L, Negley Diane L, Schmaljohn Alan L, Aman M Javad, Bavari Sina
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702-5011, USA.
Vaccine. 2004 Sep 3;22(25-26):3495-502. doi: 10.1016/j.vaccine.2004.01.063.
Ongoing outbreaks of filoviruses in Africa and concerns about their use in bioterrorism attacks have led to intense efforts to find safe and effective vaccines to prevent the high mortality associated with these viruses. We previously reported the generation of virus-like particles (VLPs) for the filoviruses, Marburg (MARV) and Ebola (EBOV) virus, and that vaccinating mice with Ebola VLPs (eVLPs) results in complete survival from a lethal EBOV challenge. The objective of this study was to determine the efficacy of Marburg VLPs (mVLPs) as a potential vaccine against lethal MARV infection in a guinea pig model. Guinea pigs vaccinated with mVLPs or inactivated MARV developed MARV-specific antibody titers, as tested by ELISA or plaque-reduction and neutralization assays and were completely protected from a MARV challenge over 2000 LD50. While eVLP vaccination induced high EBOV-specific antibody responses, it did not cross-protect against MARV challenge in guinea pigs. Vaccination with mVLP or eVLP induced proliferative responses in vitro only upon re-exposure to the homologous antigen and this recall proliferative response was dependent on the presence of CD4+ T cells. Taken together with our previous work, these findings suggest that VLPs are a promising vaccine candidate for the deadly filovirus infections.
非洲持续爆发丝状病毒,以及对其可能被用于生物恐怖袭击的担忧,促使人们加紧努力寻找安全有效的疫苗,以预防与这些病毒相关的高死亡率。我们之前报道了马尔堡病毒(MARV)和埃博拉病毒(EBOV)的病毒样颗粒(VLP)的产生,并且用埃博拉病毒样颗粒(eVLP)给小鼠接种疫苗可使其在接受致死剂量的埃博拉病毒攻击后完全存活。本研究的目的是在豚鼠模型中确定马尔堡病毒样颗粒(mVLP)作为预防致死性马尔堡病毒感染的潜在疫苗的效力。通过ELISA或蚀斑减少中和试验检测,用mVLP或灭活的马尔堡病毒接种的豚鼠产生了马尔堡病毒特异性抗体滴度,并且在超过2000 LD50的马尔堡病毒攻击下得到了完全保护。虽然用eVLP接种诱导了高埃博拉病毒特异性抗体反应,但它并不能在豚鼠中交叉保护其免受马尔堡病毒的攻击。用mVLP或eVLP接种仅在再次接触同源抗原时在体外诱导增殖反应,并且这种回忆性增殖反应依赖于CD4 + T细胞的存在。结合我们之前的工作,这些发现表明VLP是用于致命丝状病毒感染的一种有前景的疫苗候选物。