NEUTRALIZING ANTIBODIES TO HIV-1 IN SERONEGATIVE VOLUNTEERS IMMUNIZED WITH RECOMBINANT GP120 FROM THE MN STRAIN OF HIV-1
NEUTRALIZING ANTIBODIES TO HIV-1 IN SERONEGATIVE VOLUNTEERS IMMUNIZED WITH RECOMBINANT GP120 FROM THE MN STRAIN OF HIV-1
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DOI：
10.1001/jama.272.6.475
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发表时间：
1994-08-10
影响因子：
120.7
通讯作者：
FAST, P
中科院分区：
文献类型：
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作者：
BELSHE, RB;GRAHAM, BS;FAST, P
客观。-为了评价重组gp120（MN rgp120）的MN菌株作为预防人类免疫缺陷病毒（HIV）的疫苗原型的安全性和免疫原性。双盲、随机、安慰剂对照研究，受试者在0、4、24和48周接种疫苗，并随访至64周。位于密苏里州圣刘易斯、田纳西州纳什维尔和纽约州罗切斯特的艾滋病疫苗评估单位进行了临床研究。实验室研究在北卡罗来纳州罗利的杜克大学进行;数据分析由位于马里兰州波托马克的EMMES公司的数据协调和分析中心进行。57人艾滋病毒血清反应阴性，在获得艾滋病毒感染的低风险，和18至60岁。将MN rgp120疫苗分别以100 μ g、300 μ g或600 μ g的剂量给予12名志愿者，12名志愿者接受300 μ g MN rgp120疫苗和300 μ g来自菌株IIIB的rgp120的疫苗的组合。9名志愿者接受单独的明矾佐剂（对照）。通过监测淋巴细胞亚群、血清肌酐和肝酶来评估安全性。使用免疫原和对应于gp120的可变区3结构域的合成肽通过酶联免疫吸附测定来测量免疫原性。功能性抗体测定包括CD4结合阻断;抗体依赖性细胞介导的细胞毒性;以及同源和异源HIV毒株的中和。未发生严重不良反应。在48名志愿者中的33名中，两剂疫苗诱导的抗体中和了同源株HIV 1/MN。三个剂量的疫苗诱导的抗体中和MN（48名志愿者中的46名），SF-2（48名志愿者中的45名）或IIIB株HIV-1（48名志愿者中的30名）。该疫苗是安全和免疫原性。多次注射疫苗扩大并增加了中和抗体反应。
Objective.-To evaluate the safety and immunogenicity of the MN strain of recombinant gp120 (MN rgpl20) as a vaccine prototype to prevent human immunodeficiency virus (HIV).Design.-Double-blind, randomized, placebo-controlled study with subjects vaccinated at 0, 4, 24, and 48 weeks and followed up through 64 weeks.Setting.-The AIDS Vaccine Evaluation Units in St Louis, Mo, Nashville, Tenn, and Rochester, NY, conducted the clinical study. Laboratory studies were conducted at Duke University, Raleigh, NC; data analysis was done by the Data Coordinating and Analysis Center at the EMMES Corporation, Potomac, Md:Participants.-Fifty-seven persons seronegative for HIV, at low risk for acquiring HIV infection, and 18 to 60 years of age.Interventions.-The MN rgpl20 vaccine was administered to 12 volunteers each in doses of 100 mu g, 300 mu g, or 600 mu g, and 12 volunteers received a combination of 300 mu g of MN rgp1 20 vaccine and 300 mu g of vaccine from rgpl20 of strain IIIB. Nine volunteers received alum adjuvant alone (control).Main Outcome Measures.-Safety was assessed by monitoring lymphocyte subsets, serum creatinine, and liver enzymes. Immunogenicity was measured by enzyme-linked immunosorbent assay using the immunogen and synthetic peptide corresponding to the variable region 3 domain of gp120. Functional antibody assays included CD4 binding blocking; antibody-dependent, cell-mediated cytotoxicity; and neutralization of homologous and heterologous HIV strains.Results.-No severe adverse reactions occurred. In 33 of 48 volunteers, two doses of vaccine induced antibodies that neutralized the homologous strain HIV1/MN. Three doses of vaccine induced antibodies that neutralized MN (in 46 of 48 volunteers), SF-2 (in 45 of 48 volunteers), or IIIB strains of HIV-1 (in 30 of 48 volunteers).Conclusion.-The vaccines were safe and immunogenic. Multiple injections of vaccine broadened and increased the neutralizing antibody response.