A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals.
A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals.
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针对埃博拉病毒的副粘病毒载体鼻内疫苗在载体免疫动物中具有免疫原性。
DOI：
10.1016/j.virol.2008.04.029
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Bukreyev,Alexander
中科院分区：
文献类型：
--
作者：
Yang,Lijuan;Sanchez,Anthony;Ward,JerroldM;Murphy,BrianR;Collins,PeterL;Bukreyev,Alexander
埃博拉病毒（EBOV）会导致人类爆发高度致命的出血热。该病毒可以通过直接接触和气溶胶传播，被认为是一种潜在的生物武器。由于呼吸道的直接免疫对于粘膜表面的感染特别有效，因此我们之前开发了一种基于表达 EBOV 糖蛋白 GP (HPIV3/EboGP) 的具有复制能力的人副流感病毒 3 型 (HPIV3) 的鼻内疫苗，并证明它具有免疫原性，并能针对高剂量肠外 EBOV 攻击提供保护。然而，由于成年人群对 HPIV3（一种常见的人类病原体）具有相当大的免疫力，因此疫苗在该人群中的复制和免疫原性可能会受到极大限制。事实上，在本研究中，发现疫苗在 HPIV3 免疫豚鼠呼吸道中的复制被限制在不可检测的水平。这种限制似乎是基于中和抗体和 HPIV3 免疫的细胞或其他成分。令人惊讶的是，尽管 HPIV3/EboGP 的复制在 HPIV3 免疫动物中受到高度限制，但它诱导了高水平的 EBOV 特异性抗体，几乎与在 HPIV3 未接触过的动物中获得的抗体水平相同。我们还表明，先前证明的载体颗粒中功能性 GP 的存在与 HPIV3 首次接触的豚鼠呼吸道内复制的增加或呼吸道外的扩散无关，表明这种全身性病毒的附着/渗透糖蛋白的表达和功能掺入不会介导组织向性的变化。
Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans. The virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. Because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (HPIV3) expressing EBOV glycoprotein GP (HPIV3/EboGP) and showed that it is immunogenic and protective against a high dose parenteral EBOV challenge. However, because the adult human population has considerable immunity to HPIV3, which is a common human pathogen, replication and immunogenicity of the vaccine in this population might be greatly restricted. Indeed, in the present study, replication of the vaccine in the respiratory tract of HPIV3-immune guinea pigs was found to be restricted to undetectable levels. This restriction appeared to be based on both neutralizing antibodies and cellular or other components of the immunity to HPIV3. Surprisingly, even though replication of HPIV3/EboGP was highly restricted in HPIV3-immune animals, it induced a high level of EBOV-specific antibodies that nearly equaled that obtained in HPIV3-naive animals. We also show that the previously demonstrated presence of functional GP in the vector particle was not associated with increased replication in the respiratory tract nor with spread beyond the respiratory tract of HPIV3-naive guinea pigs, indicating that expression and functional incorporation of the attachment/penetration glycoprotein of this systemic virus did not mediate a change in tissue tropism.