抗艾滋病病毒疫苗研究现状(摘要)

A Way Leading to An Effective Anti-HIV Vaccine

发现艾滋病病毒（HIV）已有近30年,尽管其他病毒性疾病（如脊髓灰质炎、麻疹、腮腺炎、风疹、乙型病毒性肝炎和流行性感冒等）的疫苗研究都取得了成功,研制有效的抗HIV疫苗却一直未能有所突破。和其他感染性病毒相比,HIV具有一些独特的特性,使其疫苗研发面临更大的挑战。HIV主要感染免疫系统,尤其是特异性地攻击CD4＋T淋巴细胞,具有逃避免疫清除的一些机制,同时还可以通过整合到宿主的染色体中建立1种潜伏的贮库。

Despite the significant progress on other viral diseases such as polio,measles,mumps,rubella,hepatitis B,and influenza,creating an effective anti-HIV vaccine has become difficult in spite of the discovery of the causative agent nearly three decades ago.Compared with other infectious viruses,several distinct properties of HIV-1 make this virus a more difficult challenge for vaccine development.HIV is an infection of the immune system,especially targeting CD4＋ T lymphocytes,HIV has evolved strategies to avoid immuneelimination,and it can also establish a latent reservoir of infected lymphotes byintegration of its genome into the host chromosome.Of equal or even greater challenge facing the development of effective vaccine is the extreme diversity of HIV-1 due to its high rate of mutation and recombination.There are two types of HIV resulting from distinct zoonotic introductions：HIV-1,predominant throughout the world,and HIV-2,found primarily in West/Central Africa.At least two to three separate zoonotic jumps from chimpanzees into humans led to the disproportionate spread of HIV-1 groups M（main）,O（outlier）,and N（ono-M/ono-O）.Group M is further subdivided into nine distinct subtypes and numerous additional circulating recombinant forms.Viruses within the same subtype may differ by up to 20%,and in places such as Africa where there are multiple subtypes,circulating viruses can differ within the highly variable envelope protein by up to 38%.Indeed,the amount of HIV diversity within a single infected individual can exceed the variability generated over the course of a global influenza epidemic,the latter of which results in the need for a new vaccine each year.With more than 33 million people currently infected with HIV,HIV sequence diversity alone represents a staggering challenge on development of vaccine development,diagnosis,and treatment.However,we believe that even though HIV-1 evolution is continous resulting in an accumulation of mutations in hypervariable regions （e.g.env）,there are still a finite number of genotypes necessary for functional viral proteins and infectivity.Therefore,theoretically,a pool of Abs and T cell immune responses targeting variable regions of all （or most） HIV-1 isolates should have broadly anti-HIV activity to overcome this viral diversity.In order to carry out these goals,we have developed a series of tools,such as HIVenv recombination system to produce the pure HIV envelope recombinants,an infectious SHIVenv virus production system,and huCD4/huCCR5 B cell transgenic mouse model/293TTK/env cell line for screening broadly neutralizing anti-HIV antibody producing hybridoma cells,and a novel HIV vaccine vector system to elicit both humoral and cellular immune responses.With the combination of all of these strategies,we hope there will be a chance for us to develop an effective anti-HIV vaccine.