Human Immunodeficiency Virus Type 1 Superinfection Occurs despite Relatively Robust Neutralizing Antibody Responses
Human Immunodeficiency Virus Type 1 Superinfection Occurs despite Relatively Robust Neutralizing Antibody Responses
复制标题
DOI：
10.1128/jvi.01730-08
复制
发表时间：
2008-12-15
影响因子：
5.4
通讯作者：
Overbaugh, Julie
中科院分区：
文献类型：
--
作者：
Blish, Catherine A.;Dogan, Ozge C.;Overbaugh, Julie
第二种人类免疫缺陷病毒1型(HIV-1)毒株的重叠感染表明，在自然感染期间出现了保护性免疫的缺口。为了确定HIV-1特异性中和抗体(NAB)在这一环境中的作用，我们检测了6名在初次感染后1至5年内重叠感染的女性的NAB反应，与18名没有类似危险因素的女性进行了比较。虽然重叠感染的个体在感染后1年的NAB宽度比对照组小，但在第二次感染之前没有观察到NAB反应的宽度或效力有显著差异。事实上，六名受试者中有四名在感染第二种毒株之前有相对广泛和有效的NAB反应。为了更具体地检测NAB对超级感染病毒的特异性，从六个个体中的五个个体中克隆了这些变体。与无血缘关系的HIV感染者的血浆池相比，超级感染变种似乎没有天生的中和抵抗力。此外，重复感染的个体能够在再次感染后对这些变体产生自体NAB反应。此外，大多数重复感染的人在再次感染之前都有可以中和第二种病毒株的nabs，这表明在自然感染期间产生的nabs水平不足以阻止感染。这些数据表明，与HIV-1感染者相比，通过接种疫苗预防感染可能需要更广泛和更有效的NAB反应。
Superinfection by a second human immunodeficiency virus type 1 (HIV-1) strain indicates that gaps in protective immunity occur during natural infection. To define the role of HIV-1-specific neutralizing antibodies (NAbs) in this setting, we examined NAb responses in 6 women who became superinfected between similar to 1 to 5 years following initial infection compared to 18 women with similar risk factors who did not. Although superinfected individuals had less NAb breadth than matched controls at similar to 1 year postinfection, no significant differences in the breadth or potency of NAb responses were observed just prior to the second infection. In fact, four of the six subjects had relatively broad and potent NAb responses prior to infection by the second strain. To more specifically examine the specificity of the NAbs against the superinfecting virus, these variants were cloned from five of the six individuals. The superinfecting variants did not appear to be inherently neutralization resistant, as measured against a pool of plasma from unrelated HIV-infected individuals. Moreover, the superinfected individuals were able to mount autologous NAb responses to these variants following reinfection. In addition, most superinfected individuals had NAbs that could neutralize their second viral strains prior to their reinfection, suggesting that the level of NAbs elicited during natural infection was not sufficient to block infection. These data indicate that preventing infection by vaccination will likely require broader and more potent NAb responses than those found in HIV-1-infected individuals.