Roberts A, Buonocore L, Price R, Forman J, Rose J K
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Virol. 1999 May;73(5):3723-32. doi: 10.1128/JVI.73.5.3723-3732.1999.
We showed previously that a single intranasal vaccination of mice with a recombinant vesicular stomatitis virus (VSV) expressing an influenza virus hemagglutinin (HA) protein provided complete protection from lethal challenge with influenza virus (A. Roberts, E. Kretzschmar, A. S. Perkins, J. Forman, R. Price, L. Buonocore, Y. Kawaoka, and J. K. Rose, J. Virol. 72:4704-4711, 1998). Because some pathogenesis was associated with the vector itself, in the present study we generated new VSV vectors expressing HA which are completely attenuated for pathogenesis in the mouse model. The first vector has a truncation of the cytoplasmic domain of the VSV G protein and expresses influenza virus HA (CT1-HA). This nonpathogenic vector provides complete protection from lethal influenza virus challenge after intranasal administration. A second vector with VSV G deleted and expressing HA (DeltaG-HA) is also protective and nonpathogenic and has the advantage of not inducing neutralizing antibodies to the vector itself.
我们之前表明，用表达流感病毒血凝素（HA）蛋白的重组水疱性口炎病毒（VSV）对小鼠进行单次鼻内接种，可提供完全保护，使其免受流感病毒的致死性攻击（A. Roberts、E. Kretzschmar、A. S. Perkins、J. Forman、R. Price、L. Buonocore、Y. Kawaoka和J. K. Rose，《病毒学杂志》72:4704 - 4711，1998年）。由于某些发病机制与载体本身有关，在本研究中，我们构建了新的表达HA的VSV载体，这些载体在小鼠模型中对发病机制完全减毒。第一个载体对VSV G蛋白的胞质结构域进行了截短，并表达流感病毒HA（CT1 - HA）。这种无致病性的载体在鼻内给药后可提供完全保护，使其免受致死性流感病毒攻击。第二个载体缺失VSV G并表达HA（DeltaG - HA），同样具有保护作用且无致病性，其优点是不会诱导针对载体本身的中和抗体。
