附AIDSandHIV__培训课件.ppt

* When developing a new antiretroviral (ARV) therapy, we must look at targeting the three factors that play a role in treatment success: The virus, the drug and the patient. The high replication rate of HIV, in conjunction with the low fidelity of the replicative process, gives rise to mutant viral strains. This has important implications for the emergence of drug resistance, and highlights the need for maximally suppressive therapies; if the virus cannot replicate, it cannot mutate. Potency and durability of a drug regimen are two essential goals. High drug levels are key to achieving these aims, preventing replication of virus throughout the entire dosing interval. If drug levels are high, this ‘forgiving’ pharmacokinetic profile minimizes the impact of variability in absorption or adherence. Pre-existing mutant strains may also be suppressed by these high drug levels. Having pinpointed the improvements required for new ARV agents, it must not be forgotten that a drug will only be effective if the patient is willing to take it. Good adherence to an ARV regimen is now recognized as being vital for therapeutic success, and patients will be more likely to adhere to a drug if it causes fewer side-effects and has a convenient dosing schedule. 1 * * 注释Note： Adult prevalence rate：成人流行率 not available：不详 一些南部非洲国家中15％－36％的人患病 * * * * * 艾滋病毒疫苗 基因工程疫苗 合成肽疫苗 基因工程亚单位疫苗 病毒样颗粒疫苗 DNA疫苗 活载体疫苗 传统疫苗 减毒活疫苗 灭活疫苗 中国开发的主要人类疫苗和产量 1、合成肽疫苗(Chemically synthesized peptide) V3肽是表面蛋白GP120的可变性表位，经修饰后可诱导细胞免疫应答 可通过应用多抗原(MAP)或者通过脂肽增强其作用 连在载体蛋白上的MAP肽及V3肽已进行Ⅰ、Ⅱ期临床实验 免疫原性较差，未观察到明显效果 2、亚单位疫苗（Subunit Vaccines） mRNA cDNA Express plasmid mRNA protein HIV-1 vaccine raised in yeast 酵母 Subunit vaccine 包膜蛋白只诱导产生中和实验室毒株的抗体，该 抗体却不能中和原始毒株，部份人仍感染HIV 不管是否使用佐剂,都不能诱生细胞毒性T细胞 一般认为：此类疫苗，绝对安全，几乎无一有效 Based on gp160/gp120 All safe None effective 3、活载体疫苗（Subunit in Vector） 金丝雀病毒带有HIV gag, env, pol, nef基因 牛痘病毒带有env, gag,pol基因 伤寒沙门氏菌带有env基因 已进行Ⅰ、Ⅱ临床实验的疫苗 其的缺点为来自活载体本身的对机体的副作用