Etemad Behzad, Batra Gaurav, Raut Rajendra, Dahiya Satinder, Khanam Saima, Swaminathan Sathyamangalam, Khanna Navin
Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Am J Trop Med Hyg. 2008 Sep;79(3):353-63.
There is currently no vaccine to prevent dengue (DEN) virus infection, which is caused by any one of four closely related serotypes, DEN-1, DEN-2, DEN-3, or DEN-4. A DEN vaccine must be tetravalent, because immunity to a single serotype does not offer cross-protection against the other serotypes. We have developed a novel tetravalent chimeric protein by fusing the receptor-binding envelope domain III (EDIII) of the four DEN virus serotypes. This protein was expressed in the yeast, Pichia pastoris, and purified to near homogeneity in high yields. Antibodies induced in mice by the tetravalent protein, formulated in different adjuvants, neutralized the infectivity of all four serotypes. This, coupled with the high expression potential of the P. pastoris system and easy one-step purification, makes the EDIII-based recombinant protein a potentially promising candidate for the development of a safe, efficacious, and inexpensive, tetravalent DEN vaccine.
目前尚无预防登革热（DEN）病毒感染的疫苗，该病毒由四种密切相关的血清型（DEN-1、DEN-2、DEN-3或DEN-4）中的任何一种引起。登革热疫苗必须是四价的，因为对单一血清型的免疫不能提供针对其他血清型的交叉保护。我们通过融合四种登革热病毒血清型的受体结合包膜结构域III（EDIII），开发了一种新型四价嵌合蛋白。该蛋白在毕赤酵母中表达，并以高产率纯化至近乎同质。用不同佐剂配制的四价蛋白在小鼠体内诱导产生的抗体中和了所有四种血清型的感染性。这一点，再加上毕赤酵母系统的高表达潜力和简便的一步纯化方法，使得基于EDIII的重组蛋白成为开发安全、有效且廉价的四价登革热疫苗的潜在有前景的候选物。
