Enhancement of protection against various microbial infection by the modification of dominance of Thl or Th2 immune responses

为探讨新型DNA疫苗对假单胞菌、HIV和流感病毒感染的保护诱导作用，进行了一项实验。疫苗是通过插入编码病原生物各种保护性抗原的基因来构建的。此外，我们还利用人源化的椰子合成了DNA。对于HIV疫苗，按照给药方法进行了有效性、免疫原性和安全性的检查。为了做到这一点，编码HIV-1抗原表位的18个基因被串联起来，每个基因由大约15个氨基酸组成。对给怀孕动物接种DNA疫苗是否会由于胎盘渗透而在后代中诱导更高的免疫原性进行了研究。结果表明，在子代中有较高的免疫原性。此外，不同的DNA疫苗口服、鼻腔、经皮、静脉和直肠给药方式对粘膜免疫、局部免疫和全身免疫均有不同的效果。在流感病毒疫苗的研究中，为了激活CTL反应，我们构建了表达病毒核心蛋白M蛋白的M基因表达载体。这种DNA疫苗被证明对使用各种流感病毒的挑战是有效的。这些结果高度暗示，这些所谓的人源化密码子多价DNA疫苗将对各种微生物有效，并将成为下一代的疫苗。

An experiment was conducted to test the possibility of protection inducement by a new type of DNA vaccine against Pseudomonas, HIV and influenza virus infection. The vaccine was constructed by inserting genes, which code the various protective antigens of the pathogenic organism. In addition, we synthesized DNA by using humanized codons.For the HIV vaccine, an examination was conducted to check the efficacy, immunogenicity and safety according to the method of medication. In order to do this the 18 genes that code HIV-1 antigenic epitopes, each made of about 15 amino acids, were connected in series. Investigations were made as to whether administrating DNA vaccine to pregnant animals will induce a higher immunogenicity in the offspring due to placental penetration. Results suggesting a possibility of higher immunogenicity in the offspring were obtained. Moreover, varying the administration method of the DNA vaccine by i.e. oral, intranasal, percutaneous, intravenous and rectal showed different results in mucosal, local and systemic immunities. In the research of the influenza virus vaccine, with the view to activate the CTL response,we constructed M gene plasmid that expresses the M protein which is the core of the virus. This DNA vaccine was revealed to be effective against the challenge using various influenza viruses. These results are highly suggestive that these so-called "humanized codon multivalent DNA vaccines" will be effective against various microorganisms and will be a vaccine for the next generation.