Xiao Yuhong, Aldaz-Carroll Lydia, Ortiz Alexandra M, Whitbeck J Charles, Alexander Edward, Lou Huan, Davis Heather L, Braciale Thomas J, Eisenberg Roselyn J, Cohen Gary H, Isaacs Stuart N
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6073, USA.
Vaccine. 2007 Jan 26;25(7):1214-24. doi: 10.1016/j.vaccine.2006.10.009. Epub 2006 Oct 17.
The heightened concern about the intentional release of variola virus has led to the need to develop safer smallpox vaccines. While subunit vaccine strategies are safer than live virus vaccines, subunit vaccines have been hampered by the need for multiple boosts to confer optimal protection. Here we developed a protein-based subunit vaccine strategy that provides rapid protection in mouse models of orthopoxvirus infections after a prime and single boost. Mice vaccinated with vaccinia virus envelope proteins from the mature virus (MV) and extracellular virus (EV) adjuvanted with CpG ODN and alum were protected from lethal intranasal challenge with vaccinia virus and the mouse-specific ectromelia virus. Organs from mice vaccinated with three proteins (A33, B5 and L1) and then sacrificed after challenge contained significantly lower titers of virus when compared to control groups of mice that were not vaccinated or that received sub-optimal formulations of the vaccine. Sera from groups of mice obtained prior to challenge had neutralizing activity against the MV and also inhibited comet formation indicating anti-EV activity. Long-term partial protection was also seen in mice challenged with vaccinia virus 6 months after initial vaccinations. Thus, this work represents a step toward the development of a practical subunit smallpox vaccine.
对天花病毒故意释放的高度关注导致了开发更安全的天花疫苗的需求。虽然亚单位疫苗策略比活病毒疫苗更安全，但亚单位疫苗因需要多次加强免疫以提供最佳保护而受到阻碍。在此，我们开发了一种基于蛋白质的亚单位疫苗策略，在初次免疫和单次加强免疫后，能在正痘病毒感染的小鼠模型中提供快速保护。用来自成熟病毒（MV）和细胞外病毒（EV）的痘苗病毒包膜蛋白与CpG ODN和明矾佐剂联合接种的小鼠，可免受痘苗病毒和小鼠特异性埃可病毒的致命鼻内攻击。与未接种疫苗或接受次优疫苗配方的对照组小鼠相比，接种三种蛋白质（A33、B5和L1）然后在攻击后处死的小鼠器官中病毒滴度显著降低。攻击前从小鼠组获得的血清对MV具有中和活性，并且还抑制彗星形成，表明具有抗EV活性。在初次接种疫苗6个月后用痘苗病毒攻击的小鼠中也观察到长期的部分保护作用。因此，这项工作朝着开发实用的亚单位天花疫苗迈出了一步。
