Swenson Dana L, Warfield Kelly L, Larsen Tom, Alves D Anthony, Coberley Sadie S, Bavari Sina
US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702-5011, USA.
Expert Rev Vaccines. 2008 May;7(4):417-29. doi: 10.1586/14760584.7.4.417.
Virus-like particle (VLP)-based vaccines have the advantage of being morphologically and antigenically similar to the live virus from which they are derived. Expression of the glycoprotein and VP40 matrix protein from Lake Victoria marburgvirus (MARV) results in spontaneous production of VLPs in mammalian cells. Guinea pigs vaccinated with Marburg virus VLPs (mVLPs) or inactivated MARV (iMARV) develop homologous humoral and T-cell responses and are completely protected from a lethal homologous MARV challenge.
AIMS & METHODS: To determine whether mVLPs based on the Musoke (aka Lake Victoria) isolate of MARV could broadly protect against diverse isolates of MARV, guinea pigs were vaccinated with mVLPs or iMARV-Musoke and challenged with MARV-Musoke, -Ravn or -Ci67.
Prior to challenge, the mVLP- and iMARV-vaccinated guinea pigs had high levels of homologous MARV-Musoke and heterologous MARV-Ravn and -Ci67 antibodies. The Musoke-based mVLPs and iMARV vaccines provided complete protection in guinea pigs against viremia, viral replication and pathological changes in tissues, and lethal disease following challenge with MARV-Musoke, -Ravn or -Ci67. Guinea pigs vaccinated with RIBI adjuvant alone and infected with guinea pig-adapted MARV-Musoke, -Ravn or -Ci67 had histopathologic findings similar to those seen in the nonhuman primate model for MARV infection. Based on the strong protection observed in guinea pigs, we next vaccinated cynomolgus macaques with Musoke-based mVLPs and showed the VLP-vaccinated monkeys were broadly protected against three isolates of MARV (Musoke, Ravn and Ci67).
Musoke mVLPs are effective at inducing broad heterologous immunity and protection against multiple MARV isolates.
基于病毒样颗粒（VLP）的疫苗具有形态和抗原性与所衍生的活病毒相似的优势。维多利亚湖马尔堡病毒（MARV）的糖蛋白和VP40基质蛋白表达会导致哺乳动物细胞中自发产生VLP。用马尔堡病毒VLP（mVLP）或灭活的MARV（iMARV）接种的豚鼠会产生同源体液和T细胞反应，并能完全抵御致死性同源MARV攻击。
为了确定基于MARV穆索凯（又名维多利亚湖）分离株的mVLP是否能广泛抵御多种MARV分离株，用mVLP或iMARV - 穆索凯接种豚鼠，然后用MARV - 穆索凯、 - 拉夫恩或 - Ci67进行攻击。
在攻击前，接种mVLP和iMARV的豚鼠具有高水平的同源MARV - 穆索凯以及异源MARV - 拉夫恩和 - Ci67抗体。基于穆索凯的mVLP和iMARV疫苗为豚鼠提供了完全保护，使其免受病毒血症、病毒复制以及组织中的病理变化影响，并且在受到MARV - 穆索凯、 - 拉夫恩或 - Ci67攻击后不会患致死性疾病。单独用RIBI佐剂接种并感染适应豚鼠的MARV - 穆索凯、 - 拉夫恩或 - Ci67的豚鼠，其组织病理学结果与MARV感染的非人类灵长类动物模型中所见相似。基于在豚鼠中观察到的强大保护作用，我们接下来用基于穆索凯的mVLP接种食蟹猴，并表明接种VLP的猴子能广泛抵御三种MARV分离株（穆索凯、拉夫恩和Ci67）。
穆索凯mVLP能有效诱导广泛的异源免疫并抵御多种MARV分离株。
