Comparison of vaccine strategies using recombinant env-gag-pol MVA with or without an oligomeric env protein boost in the SHIV rhesus macaque model
Comparison of vaccine strategies using recombinant env-gag-pol MVA with or without an oligomeric env protein boost in the SHIV rhesus macaque model
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DOI：
10.1006/viro.2001.1345
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发表时间：
2002-03-15
期刊：
影响因子：
3.7
通讯作者：
Moss, B
中科院分区：
文献类型：
--
作者：
Earl, PL;Wyatt, LS;Moss, B
用表达人类免疫缺陷病毒189.6env(Env)和SIV gagpol189.6env(Env)的复制缺陷痘苗病毒(MVA)免疫恒河猴，或不加可溶性89.6env(Gp140)的蛋白佐剂免疫恒河猴。MVA/SHIV89.6单独免疫后，所有动物均产生结合性抗体，15只动物中有5只产生中和抗体，两种抗体均可通过蛋白增强而增强。此外，在MAMU-A*01阳性动物亚群中检测到CD8细胞呈CM9四聚体结合。动物被静脉注射SIV-89.6(研究1)或更致病的衍生物SIV-89.6P(研究2)。在研究1中，除一只外，所有对照和接种疫苗的动物都被感染。然而，病毒血症的水平如下(对照)。单独使用rMVA(.)RMVA+蛋白。免疫组和对照组之间差异有统计学意义，但两免疫组之间差异无统计学意义。在研究2中，所有动物都被感染了；然而，与对照组相比，接种疫苗组的高峰病毒血症减少了5倍，急性期病毒血症减少了10倍。在Challenger之后10个月，所有对照组都需要安乐死。在这两项研究中，都观察到了疫苗诱导的抗体效价和病毒负荷减少之间的关系。因此，单独用MVA/SHIV89.6免疫或用蛋白增强免疫都能刺激免疫系统的两个手臂，并显著控制病毒血症，并在用SIV-89.6P攻击后延缓疾病的进展。(C)2002年埃尔塞维尔科学公司(美国)。
Rhesus macaques were immunized with a replication-deficient vaccinia virus (MVA) expressing human immunodeficiency virus type 1 89.6 envelope (env) and SIV gagpol (MVA/SHIV89.6) with or without a protein boost consisting of soluble 89.6 env (gp140). Immunization with MVA/SHIV89.6 alone elicited binding antibodies in all animals and neutralizing antibodies in 5 of 15 animals, Both types of antibodies were enhanced by protein boosting In addition, CD8 cells exhibiting CM9 tetramer binding were detected in the subset of animals that were Mamu-A*01 positive. Animals were challenged intravenously with either SHIV-89.6 (Study 1) or the more pathogenic derivative SHIV-89.6P (Study 2). In Study 1, all control and vaccinated animals except one became infected. However, the levels of viremia were as follows controls (.) rMVA alone (.) rMVA + protein. The differences were statistically significant between immunized and control groups but not between the two immunized groups. In Study 2, all animals became infected; however, the vaccinated group exhibited a 5-fold reduction in peak viremia and a 10-fold reduction in the postacute phase viremia in comparison to the controls All of the controls required euthanasia by 10 months after challenger A relationship between vaccine-induced antibody titers and reduction in virus burden was observed in both studies. Thus, immunization with MVA/SHIV89.6 alone or with a protein boost stimulated both arms of the immune system and resulted in significant control of viremia and delayed progression to disease after challenge with SHIV-89.6P. (C) 2002 Elsevier Science (USA).