TESTING IN MONKEYS OF CANDIDATE VACCINES FOR SAIDS

SIV表达载体的细胞内递送 Accell TM基因枪对恒河猴表皮的诱导作用 在诱导显著的免疫球蛋白反应方面。这些回应是 在加强免疫后显著提高 重组痘苗病毒。三只猴子身上有几只 连续剂量的编码SIVmac239 gp120和gp160的DNA被开发出来 最高免疫球蛋白滴度约为1：20,000。在一首单曲之后 表达重组痘苗病毒活疫苗的加强免疫 SIVmac239和gp160，这些动物出现了瞬时峰值终点 效价：1：2x106。这些反应大大高于 在注射了DNA或牛痘疫苗的动物身上发现的这些病毒 仅载体一项。此外，一群最先被引爆的动物 表达SIVmac239 gp160或SIV的痘苗病毒 DeltaB670 gp160或两者的组合也出现了类似的情况 用DNA单次加强免疫后的反应， 论证了协同效应不依赖于 疫苗接种顺序。所有疫苗接种组和5名对照组 加强免疫后19周经静脉注射激发 用10种最低剂量的SIVdeltaB670进行挑战。活力四射 加强免疫后的抗体反应不持久 已降至约1：3,000至1：35,000的滴度 挑战的时刻。经聚合酶链式反应检测，所有动物均被感染。 PBMC DNA在挑战后14天证明疫苗没有 诱导无菌免疫力。病毒载量，中和抗体， 聚合酶链式反应、血浆抗原血症、酶联免疫吸附试验和临床检查 被用来监测挑战后的保护水平。

Intracellular delivery of SIV expression vectors into the epidermis of rhesus macaques using the AccellTM gene-gun resulted in in the induction of significant IgG responses. These responses were dramatically elevated following a booster immunization with a recombinant vaccinia virus. Three monkeys primed with several consecutive doses of DNA encoding SIVmac239 gp120 and gp160 developed maximum IgG titers of approximately 1:20,000. Following a single booster immunization with a live recombinant vaccinia virus expressing SIVmac239 and gp160, these animals developed transient peak endpoint titers of >1:2x106. These responses were dramatically higher than those seen in animals primed and boosted with either DNA or vaccinia vectors alone. In addition, a group of animals that were first primed with a vaccinia virus expressing either SIVmac239 gp160, or SIV deltaB670 gp160 or a combination of both, also developed similar responses following a single booster immunization with DNA, demonstrating that the synergistic effect is not dependent on the order of vaccine administration. All vaccinates and 5 controls were challenged 19 weeks after the booster immunization by intravenous challenge with 10 minimum infectious doses of SIVdeltaB670. Vigorous antibody responses after the booster immunization were not persistent and had fallen to titers of approximately 1:3,000 to 1:35,000 at the time of challenge. All animals were infected as determined by PCR of PBMC DNA14 days post-challenge demonstrating the vaccines did not induce sterilizing immunity. Virus loads, neutralizing antibodies, PCR, plasma antigenemia, ELISAs, and clinical examinations were employed to monitor the level of protection post-challenge.