Cornelissen Marion, Euler Zelda, van den Kerkhof Tom L G M, van Gils Marit J, Boeser-Nunnink Brigitte D M, Kootstra Neeltje A, Zorgdrager Fokla, Schuitemaker Hanneke, Prins Jan M, Sanders Rogier W, van der Kuyl Antoinette C
1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
2 Department of Experimental Immunology, Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
AIDS Res Hum Retroviruses. 2016 Oct/Nov;32(10-11):1135-1142. doi: 10.1089/aid.2015.0324. Epub 2016 Feb 24.
The effect of serial HIV-1 infection on the development of the broadly neutralizing antibody (bNAb) response was studied in an individual, H01-10366, with a serial HIV-1 superinfection (SI), hence triple infection, and compared with the bNAb response in three superinfected as well as 11 monoinfected men who have had sex with men (MSM) from Amsterdam, the Netherlands. Neutralization assays measuring heterologous neutralizing antibody (NAb) titers on a panel of six representative viruses from different HIV-1 subtypes were performed on blood serum samples obtained ∼3 years after primary HIV infection (PHI) and longitudinally for H01-10366. A bNAb response was defined as having a geometric mean neutralization titer (the reciprocal serum dilution giving 50% inhibition of virus infection, inhibitory dilution (ID)) ≥100 and neutralizing >50% of viruses in the panel with an ID titer ≥100. H01-10366 quickly developed a potent NAb response against subtype B viruses before subtype B SI, but no broadening of the response occurred after the second subtype B infection or the third infection with CRF01_AE. When comparing H01-10366 with matched monoinfected (N = 11) and superinfected (N = 3) individuals analyzed 3 years after PHI, we found that 5 of the 15 individuals (4/11 monoinfected, 1/4 SI) developed a bNAb response. However, there was no statistically discernible difference between the bNAb response and HIV-1 SI. Thus, HIV-1 SI was not associated with the breadth and potency of the bNAb response in this small group of Dutch MSM with SI that included a triple HIV-1-infected individual.
在一名编号为H01 - 10366的个体中研究了HIV - 1连续感染对广泛中和抗体（bNAb）反应发展的影响，该个体发生了HIV - 1连续重复感染（SI），即三重感染，并将其与来自荷兰阿姆斯特丹的3名重复感染以及11名男男性行为者（MSM）单感染个体的bNAb反应进行了比较。对原发性HIV感染（PHI）后约3年获得的血清样本进行中和试验，以测量针对一组来自不同HIV - 1亚型的六种代表性病毒的异源中和抗体（NAb）滴度，并对H01 - 10366进行纵向检测。bNAb反应定义为几何平均中和滴度（能使病毒感染抑制50%的血清稀释倍数，即抑制性稀释度（ID））≥100，且ID滴度≥100时能中和该组中>50%的病毒。H01 - 10366在B亚型SI之前迅速产生了针对B亚型病毒的强效NAb反应，但在第二次B亚型感染或第三次CRF01_AE感染后反应并未拓宽。当将H01 - 10366与PHI后3年分析的匹配单感染（N = 11）和重复感染（N = 3）个体进行比较时，我们发现15名个体中有5名（11名单感染个体中的4名，4名重复感染个体中的1名）产生了bNAb反应。然而，bNAb反应与HIV - 1 SI之间没有统计学上可辨别的差异。因此，在这一小群包括一名三重HIV - 1感染个体的荷兰重复感染MSM中，HIV - 1 SI与bNAb反应的广度和效力无关。
