Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
Vaccine. 2012 Oct 5;30(45):6402-8. doi: 10.1016/j.vaccine.2012.08.018. Epub 2012 Aug 22.
We previously demonstrated that recombinant raccoonpox (RCN) virus could serve as a vector for an influenza vaccine. RCN constructs expressing the hemagglutinin (HA) from H5N1 viruses were immunogenic in chickens. In the current study, we generated several recombinant RCN constructs expressing influenza (H5N1) antigens and a molecular adjuvant (Heat-Labile enterotoxin B from E. coli: RCN-LTB), demonstrated their expression in vitro, and evaluated their ability to protect mice against H5N1 virus challenge. RCN-HA provided strong protection when administered intradermally (ID), but not intranasally (IN). Conversely, the RCN-neuraminidase (NA) construct was highly efficacious by the IN route and elicited high titers of neutralizing antibodies in mice. Vaccination by combined ID (RCN-HA) and IN (RCN-NA) routes offered mice the best protection against an IN challenge with heterologous H5N1 virus. However, protection was reduced when the different RCN constructs were pre-mixed, perhaps due to reduced expression of antigen.
我们之前证明重组浣熊痘（RCN）病毒可以作为流感疫苗的载体。表达 H5N1 病毒血凝素（HA）的 RCN 构建体在鸡中具有免疫原性。在当前的研究中，我们生成了几种表达流感（H5N1）抗原和分子佐剂（大肠杆菌不耐热肠毒素 B：RCN-LTB）的重组 RCN 构建体，证明了它们在体外的表达，并评估了它们保护小鼠免受 H5N1 病毒攻击的能力。RCN-HA 经皮（ID）给药时提供了强大的保护作用，但经鼻（IN）给药时则没有。相反，RCN-神经氨酸酶（NA）构建体通过 IN 途径具有高度的功效，并在小鼠中引发了高滴度的中和抗体。通过 ID（RCN-HA）和 IN（RCN-NA）联合途径接种可为 IN 挑战提供最佳保护，免受异源 H5N1 病毒的侵害。然而，当不同的 RCN 构建体预先混合时，保护作用会降低，这可能是由于抗原表达减少所致。
