IMMUNIZATION OF CHIMPANZEES CONFERS PROTECTION AGAINST CHALLENGE WITH HUMAN-IMMUNODEFICIENCY-VIRUS
IMMUNIZATION OF CHIMPANZEES CONFERS PROTECTION AGAINST CHALLENGE WITH HUMAN-IMMUNODEFICIENCY-VIRUS
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DOI：
10.1073/pnas.88.2.542
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发表时间：
1991-01-01
影响因子：
11.1
通讯作者：
FULTZ, PN
中科院分区：
文献类型：
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作者：
GIRARD, M;KIENY, MP;FULTZ, PN
在连续注射来自 HIV-1 BRU 毒株的不同人类免疫缺陷病毒 1 (HIV-1) 抗原制剂后，三只黑猩猩体内产生了持续高滴度的中和抗体，其中包括完整的灭活病毒或纯化的重组蛋白，然后是与主要 HIV-1 中和表位 V3 相同的合成肽。 对动物进行静脉注射挑战。使用 40 个黑猩猩感染剂量（相当于 100 个组织培养物 50% 感染剂量）的 HIV-1 IIIB 分离株库存。 6个月的随访后，根据血清学和病毒学标准，包括聚合酶链式反应分析以及未能从外周血淋巴细胞、骨髓和淋巴结组织中分离出病毒，所有三只动物均未受到感染。 在监测了 1 年的两只黑猩猩中，最初在 32 周时从一只动物中分离出病毒，但第二只黑猩猩在 12 个月内的所有检测均呈病毒阴性；第三只动物在 9 个月的随访中病毒呈阴性。 这些结果表明，通过免疫接种有可能引起针对HIV-1的保护或显着延迟感染，从而为HIV-1疫苗的开发奠定了基础。
Sustained high titers of neutralizing antibodies were elicited in three chimpanzees after sequential injections of different human immunodeficiency virus 1 (HIV-1) antigen preparations derived from the HIV-1 BRU strain that included whole inactivated virus or purified recombinant proteins and then synthetic peptides identical to the major HIV-1 neutralizing epitope V3. The animals were challenged i.v. with 40 chimpanzee infectious doses (equivalent to 100 tissue culture 50% infectious doses) of a stock of HIV-1 IIIB isolate. After 6 mo of follow-up, all three animals appeared uninfected by serologic and virologic criteria, including polymerase chain reaction analysis and failure to isolate virus from peripheral blood lymphocytes, bone marrow, and lymph node tissue. Of two chimpanzees monitored for 1 yr, virus was isolated initially from one animal at 32 weeks, but the second chimpanzee was virus negative by all assays through 12 mo; the third animal has remained virus negative through 9 mo of follow-up. These results indicate that it is possible to elicit protection against, or significantly delay infection of, HIV-1 by immunization, thus laying the foundation for development of an HIV-1 vaccine.