Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1
Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1
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DOI：
10.1128/jvi.00201-06
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发表时间：
2006-06-01
影响因子：
5.4
通讯作者：
Derdeyn, Cynthia A.
中科院分区：
文献类型：
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作者：
Li, Bing;Decker, Julie M.;Derdeyn, Cynthia A.
尽管全世界大多数艾滋病病例是由c型病毒引起的，但关于c型病毒感染者中和抗体反应的信息有限。在这里，我们比较了在急性和早期感染乙型和丙型人类免疫缺陷病毒1型（HIV-1）时，自体中和抗体（NAb）对病毒包膜（Env）糖蛋白的反应过程和强度。采用假病毒报告基因测定法，在平均25个月的评估期内，对6名b亚型感染者和11名c亚型感染者的NAb应答进行了评估。C组的所有受试者都是通过异性接触感染的，而B组的6名受试者中有5名是通过男性与男性的接触感染的。NAb反应的动力学和强度在B组和C组的受试者中有所不同；然而，c型感染者血浆中抗体达到的中位50%抑制浓度（IC50滴度）总体上比b型感染者高3.5倍（P = 0.06）。与B组相比，C组病毒表面Env糖蛋白gp120 V1 - V4区氨基酸长度显著缩短（P = 0.002），其nab滴度较高。尽管自体C亚型NAb反应具有效力，但它并不针对交叉中和的表位。这些数据表明，亚型C Envs在感染早期引发了一种有效但有限的NAb反应，其IC50滴度经常超过1:10 000，这表明Env的免疫原性或对中和的易感性可能存在进化支特异性差异。
Information about neutralizing antibody responses in subtype C-infected individuals is limited, even though this viral subtype causes the majority of AIDS cases worldwide. Here we compared the course and magnitude of the autologous neutralizing antibody (NAb) response against viral envelope (Env) glycoproteins present during acute and early infection with subtypes B and C human immunodeficiency virus type 1 (HIV-1). NAb responses were evaluated in 6 subtype B-infected and 11 subtype C-infected subjects over a mean evaluation period of 25 months using a pseudovirus reporter gene assay. All subjects in the C cohort were infected through heterosexual contact, while five of the six subjects in the B cohort were infected via male-to-male contact. The kinetics and magnitude of the NAb responses varied among subjects in the B and C cohorts; however, the median 50% inhibitory concentration (IC50 titer) reached by antibody in the plasma of subtype C-infected subjects, overall, was 3.5-fold higher than in the subtype B-infected subjects (P = 0.06). The higher titers of NAbs in the C cohort were associated with viruses having significantly shorter amino acid length (P = 0.002) in the V1 to V4 region of the surface Env glycoprotein, gp120, compared to the B cohort. Despite the potency of the autologous subtype C NAb response, it was not directed against cross-neutralizing epitopes. These data demonstrate that subtype C Envs elicit a potent yet restricted NAb response early in infection that frequently reaches IC50 titers in excess of 1:1,000 and suggest that clade-specific differences may exist in Env immunogenicity or susceptibility to neutralization.