Djavani M, Yin C, Lukashevich I S, Rodas J, Rai S K, Salvato M S
Institute of Human Virology, University of Maryland Biotechnology Center, Baltimore 21201, USA.
J Hum Virol. 2001 Mar-Apr;4(2):103-8.
Lassa fever virus (LAS) is transmitted to man by rodent carriers and is fatal in a third of untreated cases. Our goal is to provide immune protection from Lassa fever by mucosal vaccination.
STUDY DESIGN/METHODS: Mice were vaccinated intragastrically with control vectors or with vectors (vaccinia or Salmonella) expressing LAS nucleocapsid protein (NP). Mice were challenged intracranially with a lethal dose of the related arenavirus, lymphocytic choriomeningitis virus (LCMV), as a measure of the vaccine's ability to elicit cross-protection.
Salmonella and vaccinia vectors expressing LAS NP each protected a third of the mice from lethal challenge with LCMV. All mice vaccinated with a vector expressing LCMV NP were protected as expected.
The LAS recombinant Salmonella vector is comparable to the LAS recombinant vaccinia vector in its ability to cross-protect mice from lethal challenge. Nucleocapsid protein is an inadequate immunogen on its own, but provides sufficient cross-protection to make it a useful component of a broadly reactive arenavirus vaccine.
拉沙热病毒(LAS)通过啮齿动物携带者传播给人类,在三分之一未经治疗的病例中是致命的。我们的目标是通过黏膜疫苗接种提供针对拉沙热的免疫保护。
研究设计/方法:用对照载体或表达LAS核衣壳蛋白(NP)的载体(痘苗病毒或沙门氏菌)对小鼠进行胃内接种。用致死剂量的相关沙粒病毒淋巴细胞性脉络丛脑膜炎病毒(LCMV)对小鼠进行颅内攻击,以此作为疫苗引发交叉保护能力的一种衡量。
表达LAS NP的沙门氏菌和痘苗病毒载体各自保护了三分之一的小鼠免受LCMV致死性攻击。所有接种表达LCMV NP载体的小鼠都如预期那样得到了保护。
LAS重组沙门氏菌载体在使小鼠免受致死性攻击的交叉保护能力方面与LAS重组痘苗病毒载体相当。核衣壳蛋白本身是一种不充分的免疫原,但能提供足够的交叉保护,使其成为一种广泛反应性沙粒病毒疫苗的有用成分。