Alphavirus replicon particles encoding the fusion or attachment glycoproteins of respiratory syncytial virus elicit protective immune responses in BALB/c mice and functional serum antibodies in rhesus
- 作者：Matthew B. Elliott ; Tong Chen ; Nicole B. Terio ; Siew-Yen Chong ; Rashed Abdullah ; Amara Luckay ; Michael A. Egan ; Lee Anne Boutilier ; Krista Melville ; Robert A. Lerch ; Deborah Long ; John. H. Eldridge ; C
- 关键词：Respiratory syncytial virus ; Vaccine ; Venezuelan equine encephalitis virus ; Alphavirus ; Replicons ; BALB/c mice ; Rhesus macaques ; Balanced immune responses ; Bronchoalveolar lavage
- 刊名：Vaccine
- 出版年：2007
- 期刊代码：89_0264410x
- 类别：imm
- 出版时间：10 October 2007
- 卷：25
- 期：41
- 页码：7132-7144
- 文件大小：364 K
摘要
Respiratory syncytial virus (RSV) is a major cause of acute respiratory tract disease in humans. Towards development of a prophylactic vaccine, we genetically engineered Venezuelan equine encephalitis virus (VEEV) replicons encoding the fusion (Fa) or attachment (Ga or Gb) proteins of the A or B subgroups of RSV. Intramuscular immunization with a formulation composed of equal amounts of each replicon particle (3vRSV replicon vaccine) generated serum neutralizing antibodies against A and B strains of RSV in BALB/c mice and rhesus macaques. When contrasted with purified natural protein or formalin-inactivated RSV formulated with alum, the 3vRSV replicon vaccine induced balanced Th1/Th2 T cell responses in mice. This was evident in the increased number of RSV-specific IFN-γ+ splenocytes following F or G peptide stimulation, diminished quantity of eosinophils and type 2 T cell cytokines in the lungs after challenge, and increased in vivo lysis of RSV peptide-loaded target cells. The immune responses in mice were also protective against intranasal challenge with RSV. Thus, the replicon-based platform represents a promising new strategy for vaccines against RSV.