疫苗革命性突破或可解决艾滋病疫苗难题

　　

生物通报道，来自丹麦哥本哈根大学的科学家近期研发出一种新型的疫苗，利用新的理论制备疫苗也许可以挽救成千上万的疾病患者，也可能是疫苗技术的一个新的里程碑。

 

研究小组的疫苗制备平台称为“Invacc”，是一个以DNA疫苗为基础的改造过的新疫苗平台，具有更强的疫苗所需的特征。这个平台包括，一个与疫苗对抗的抗原相连的氨基酸链，这个带有特殊遗传尾巴的链将插入一个流感样的病毒载体中，比如说腺病毒，将病毒注射到人体内，将有助于疫苗激起机体更强大的免疫反应，一旦有病原侵入机体，疫苗激起的免疫反应将快速地消灭该病原。

 

研究项目的领导者，Jan Pravsgaard副教授称，这是一项令人振奋的技术，疫苗平台将提供前所未有的疫苗技术，可用于制备病毒疫苗、细菌疫苗，甚至是癌症疫苗。值得关注的一点是，新的疫苗可以对付不断变异改进的病毒或是细菌。

 

研究小组进行了流感疫苗动物实验，结果表明通过新疫苗技术制备的疫苗可提供完全的保护。

 

创新之处

传统的DNA疫苗往往存在着局限，因为它们只能产生少量的重要抗原刺激机体的免疫系统。正是由于传统的DNA疫苗无法把要传递的抗原完全地传递给机体，因此不能产生有效的保护性。

 

而Invacc疫苗平台的科学家找出了一个解决该问题的绝妙方法，他们制备了一个氨基酸链，插入腺病毒载体内，这一技术促进表达更多的病原抗原，帮助免疫系统识别更多的关键抗原。

其关键的优势在于具有智能性，可识别伪装或是突变后的细菌或是病毒。

 

另外，该氨基酸链还有助于延长疫苗的有效保护期。

原文摘要：New type of vaccines delivers strong and fast immune response

http://healthsciences.ku.dk/newslist/invacc/

 

The key benefits of the new technology:

- The new platform delivers a broad and very powerful immune response, which can defeat invading pathogens.

- InVacc activates the CD4+ T cells of the immune system, which govern and coordinate the other immune system attack cells. For reasons not yet fully understood, activating the CD4+ cells enhances the response of the associated attack cells (producing large numbers of CD8+ cells) and is an important reason why the platform is able to deliver such a strong immune response.

How the new technology works

The original DNA vaccines - the precursor of the present platform - consist of a single gene taken from the virus or bacteria against which protection is sought and is injected into the body. The alien DNA is then ‘read' by the body's host cells (transcription of the gene) and is converted into pathogenic proteins. Because these pathogenic proteins (antigens) are recognised as foreign, they are placed on the surface of the cell to alert the immune system and trigger an appropriate immune response. This, at least is the idea behind the original DNA vaccines, which use the more potent ingredient of a gene rather than live, biological material to activate the immune system.

DNA vaccines, however, have so far been ineffective because, in practice, they generate too few of the all-important antigens - the ‘alarm bells' that warn the immune system of attack. This is because DNA vaccines are unable to fully decode their contents and deliver their message to the immune system. In other words, the original DNA vaccines are unable to guide the body to ‘read' and process the particular cell pieces that are carrying the DNA vaccine, which in turn would ensure that the antigens are produced.

The scientists behind InVacc, however, have come up with a means to overcome this problem. Their key innovation - the chain of amino acids inserted into the adenovirus - promotes the decoding of the new vaccines and ensures that more of the antigens are shown to the immune system. The adenovirus used for the vaccines plays a crucial role in all of this because it helps to set off the necessary chain reaction that allows the vaccine platform to work. It does this by presenting the body with a recognisable threat. ‘Primed' to react to the adenovirus, which it has been exposed to many times before, the body becomes more sensitive to and hones in on the particular pieces in the body that are carrying the adenovirus (with the DNA vaccine concealed inside) and begins processing these cell pieces.

The second important component in the vaccine platform, the amino acid chain, is now also able to work and is critical to providing long-lasting immunity from disease. The chain, made up of 215 amino acids, functions to latch onto and drag up more of the important genetic material from the vaccines to the surface of the cells, thereby ensuring that more antigens are exhibited. The greater the amount of material raised to the surface from the vaccines, the more likely that the right attack cells are activated.

"The delivery mechanism provided by the amino acids is important for several reasons", explains Associate Professor Pravsgaard. First, the amino acid chain enables the vaccines to activate different profiles of attack cells. Second, it picks up more of the important genetic information from the inner compartment of the virus or bacterium - where for our purposes - the crucial DNA material is based. Attaching DNA strands from the interior of the virus to the amino acid chain is crucial to developing stable vaccines, since it gives the immune system solid data on the nature of the threat it is faced with, even after the virus or bacteria has mutated".

Deadly pathogens such as viruses tend to mutate when they replicate and are thus able to pass under the radar of the immune system and avoid detection. "A mutated virus is a bit like a virus wearing a disguise," explains Professor Pravsgaard. "Viruses possess a special protein surface or outer shell that they constantly adapt to protect their core DNA from being damaged. However, if we can give the immune system more intelligence about the virus from its conserved interior - which is less likely to mutate - we can then communicate the true identity of the virus. It's as if we were giving the immune system a fingerprint of a criminal with several points of identification, so that it can recognize the virus, regardless of its disguise".

The scientists from the University of Copenhagen predict that the new platform will protect against the vast majority of viruses and bacteria, where a gene can be identified and targeted with a DNA vaccine. Certain cancers such as skin cancer which have a genetic basis and/or a viral profile (e.g. cervical cancer begins with infection by the human papillomavirus) would also be candidates for the vaccines.

The Scandanivan company Novo A/S and the Novo Nordisk Foundation have such faith in the new technology that they have already invested funds to create a strategic plan for development and use of the vaccine. "The grants awarded through our Novo Seeds programme are only for very select projects that show outstanding promise, explains Novo Seeds Investment Director, Stephen Christgau." "InVacc is definitely one of those. Our grants will help the team to develop and commercialise their groundbreaking research and validate the advantages of the vaccine platform against competing technologies".

Peter Holst from the research team (together with the Technical Transfer Unit) is currently also seeking backing from international funds to take the project to its next phase of development and ultimately into clinical trials.