Conley A J, Kessler J A, Boots L J, McKenna P M, Schleif W A, Emini E A, Mark G E, Katinger H, Cobb E K, Lunceford S M, Rouse S R, Murthy K K
Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
J Virol. 1996 Oct;70(10):6751-8. doi: 10.1128/JVI.70.10.6751-6758.1996.
The anti-gp41 virus neutralizing monoclonal antibody 2F5 was infused into chimpanzees, which were then given an intravenous challenge with a primary human immunodeficiency virus type I (HIV-1) isolate. In two control animals, the infection was established immediately, as evidenced by positive cell-associated DNA PCR and serum RNA PCR tests within 1 week, seroconversion by 4 weeks, and development of lymphadenopathy in this acute phase. Serum RNA PCR tests were negative in one of the two antibody-infused animals until week 8 and in the other antibody-infused animal until week 12; both animals seroconverted at week 14. The peak of measurable virus-specific serum RNA was delayed until week 16 in one antibody-infused animal. Virus-specific RNA in the other animal did not reach levels comparable to those in the other animals through 1 year of follow-up studies. Virus was isolated from the week 16 blood sample from one infused animal. Virus was not isolated from peripheral blood of the second animal but was isolated from lymph node cells taken at week 36. The infection of untreated chimpanzees with this primary isolate appears robust. Use of this isolate should widen the scope of possible experiments in the chimpanzee model. This antibody infusion study indicates that neutralizing antibody, when present at the time of challenge, affects the timing and level of infection and remains influential after it can no longer be detected in the peripheral circulation. It is possible that preexisting, neutralizing antibodies (passively administered or actively elicited) affect the course of acute-phase virus replication in humans. It remains to be established whether these immunologically mediated early effects will influence the course of HIV-1 disease.
将抗gp41病毒中和单克隆抗体2F5注入黑猩猩体内,随后用I型原发性人类免疫缺陷病毒(HIV-1)分离株对其进行静脉内攻击。在两只对照动物中,感染立即确立,1周内细胞相关DNA聚合酶链反应(PCR)和血清RNA PCR检测呈阳性、4周时血清转化以及急性期出现淋巴结病均证明了这一点。在两只注入抗体的动物中,一只在第8周前血清RNA PCR检测呈阴性,另一只在第12周前呈阴性;两只动物均在第14周时血清转化。在一只注入抗体的动物中,可测量的病毒特异性血清RNA峰值延迟至第16周。通过1年的随访研究,另一只动物中的病毒特异性RNA未达到与其他动物相当的水平。从一只注入抗体动物第16周的血样中分离出病毒。未从第二只动物的外周血中分离出病毒,但从第36周采集的淋巴结细胞中分离出病毒。用这种原发性分离株感染未治疗的黑猩猩似乎很容易成功。使用这种分离株应会扩大黑猩猩模型中可能进行的实验范围。这项抗体注入研究表明,在攻击时存在的中和抗体可影响感染的时间和程度,并且在其在外周循环中无法再被检测到之后仍具有影响力。预先存在的中和抗体(被动给予或主动诱导产生)有可能影响人类急性期病毒复制的过程。这些免疫介导的早期效应是否会影响HIV-1疾病的进程仍有待确定。