Progress In Scientific Research

SKLRD and other organizations work together to develop new technology for improving virus carrier AIDS vaccine

2015-12-17832

Recently, the State Key Laboratory of Respiratory Disease has worked with organizations such as Zhejiang University and the Academy of Military Medical Sciences to successfully develop a new technology of vaccine modification and improvement (Biomineralization-based Virus Shell-Engineering (BVSE)) with the aid of biomineralization. The research fruit was published online by Advanced Materials, a journal of material science on November 26, 2015 (http://dx.doi.org/10.1002/adma.201503740). Professor Tang Ruikang of Zhejiang University, research fellow Chen Ling of the State Key Laboratory of Respiratory Disease and Qin Chengfeng, a research fellow of the Academy of Military Medical Sciences are the corresponding authors of the paper, and Dr. Wang Xiaoyu of Zhejiang University and Dr. Sun Caijun of Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences are the first authors of this paper.

Adenovirus, particularly Ad5, has been widely used as a carrier for recombinant gene therapy and vaccine. According to statistics, Ad5 is used as a gene carrier in about 1/4 of clinical tests of gene therapy and vaccine carrier of the world, including in the research and development of new AIDS vaccines and Ebola vaccines. However, Adenovirus neutralizing antibodies commonly exist among people. For example, about 77% of Southerners are positive in Ad5 anti-body. Even if those showing a negative nature in Ad5 anti-body, after using Ad5 carrier product once, will also turn positive in Ad5 anti-body. These Adenovirus neutralizing anti-bodies have inhibited the repeated use efficiency of Adenovirus carrier vaccine or gene therapy products to a great extent.


In order to overcome the negative impact of Adenovirus neutralizing anti-body, the scientific and technical personnel of the team applied the biomineralization widely existing in the nature in the modification and improvement of the performance of vaccines. Using the Adenovirus carrier vaccine carrying AIDS antigen as the model, researchers have discovered that calcium phosphate can form a layer of mineralized film at the surface of Adenovirus under certain conditions, which seems to add a layer of shell to the virus. After a series of in vitro and in vivo experiments, it indicates that BVSE technology can effectively avoid the Adenovirus carrier vaccine from being identified by the neutralizing anti-body, effectively infect the target cells and facilitate the expression of HIV antigen gene carried. Meanwhile, they have also discovered that the Ca2+ ions carried at the surface of the vaccines treated by BVSE also function as an adjuvant, which enables the vaccine to unleash a greater potential, stimulates more effective immune response of multi-functional cells of HIV virus specificity and significantly enhances the immune effect of HIV vaccine. The research has offered a new idea for improving the use efficiency and scope of Adenovirus carrier, which is of important scientific significance and application values for the research and development of new and more effective vaccines and immune therapy strategies against AIDS, other infectious diseases and tumors.