BACKGROUND Vaccines eliciting protective and persistent immune responses against multiple human immunodeficiency virus type 1 (HIV-1) clades are needed. This study evaluated the persistence of immune responses induced by an investigational, AS01-adjuvanted HIV-1 vaccine as long as 14 years after vaccination. METHODS This phase I, open-label, descriptive, mono-centric, extension study with a single group (NCT03368053) was conducted in adults who received ≥3 doses of the clade B gp120-NefTat/AS01B vaccine candidate 14 years earlier in a previous clinical trial (NCT00434512). Binding responses of serum antibodies targeting a panel of envelope glycoproteins, including gp120, gp140 and V1V2-scaffold antigens and representative of the antigenic diversity of HIV-1, were measured by binding antibody multiplex assay (BAMA). The gp120-specific CD4+/CD8+ T-cell responses were assessed by intracellular cytokine staining assay. RESULTS At Year 14, positive IgG binding antibody responses were detected in 15 out of the 16 antigens from the BAMA V1V2 breadth panel, with positive response rates ranging from 7.1% to 60.7%. The highest response rates were observed for clade B strain V1V2 antigens, with some level of binding antibodies against clade C strains. Anti-V1V2 IgG3 response magnitude breadth, which correlated with decreased risk of infection in a previous efficacy trial, was of limited amplitude. Response rates to the antigens from the gp120 and gp140 breadth panels ranged from 7.7% to 94.1% and from 15.4% to 96.2% at Year 14, respectively. Following stimulation with gp120 peptide pool, highly polyfunctional gp120-specific CD4+ T-cells persisted up to Year 14, with high frequencies of CD40L tumor necrosis factor alpha (TNF-α), CD40L interleukin-2 (IL-2), CD40L TNF-α IL-2 and CD40L interferon gamma (IFN-γ) TNF-α IL-2 CD4+ T-cells, but no CD8+ T-cells detected. CONCLUSIONS Persistent antibodies binding to HIV-1 envelope glycoproteins, including the V1V2-scaffold, and gp120-specific cellular immunity were observed in volunteers vaccinated 14 years earlier with the gp120-NefTat/AS01B vaccine candidate.

中文翻译：

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艾滋病毒gp120-NefTat / AS01B疫苗接种后长达14年的疫苗引起的免疫反应的持续性。

背景技术需要针对多种人类免疫缺陷病毒1型（HIV-1）进化枝引起保护性和持久性免疫应答的疫苗。这项研究评估了长达14年的AS01辅助HIV-1疫苗的研究性试验诱导的免疫反应的持久性。方法该I期开放标签，描述性，单中心，单组扩展研究（NCT03368053）是在前一个14年前接受≥3剂进化枝B gp120-NefTat / AS01B候选疫苗的成年人中进行的。临床试验（NCT00434512）。通过结合抗体多重测定（BAMA）测量了针对一组包括gp120，gp140和V1V2支架抗原的包膜糖蛋白的血清抗体的结合反应，并代表了HIV-1的抗原多样性。通过细胞内细胞因子染色测定法评估gp120特异性CD4 + / CD8 + T细胞应答。结果在第14年，来自BAMA V1V2广度板块的16种抗原中有15种检测到了阳性IgG结合抗体反应，阳性反应率为7.1％至60.7％。对于进化枝B株V1V2抗原观察到最高的应答率，并且具有针对进化枝C株的一定水平的结合抗体。与以前的功效试验中降低的感染风险相关的抗V1V2 IgG3反应幅度的幅度是有限的。14年级时，gp120和gp140广度板对抗原的应答率分别为7.7％至94.1％和15.4％至96.2％。用gp120肽库刺激后，高度多功能的gp120特异性CD4 + T细胞持续存在至14年 具有高频率的CD40L肿瘤坏死因子α（TNF-α），CD40L IL-2（IL-2），CD40LTNF-αIL-2和CD40L干扰素γ（IFN-γ）TNF-αIL-2 CD4 + T-细胞，但未检测到CD8 + T细胞。结论在14年前接种gp120-NefTat / AS01B候选疫苗的志愿者中观察到了与HIV-1包膜糖蛋白（包括V1V2-支架）结合的持久性抗体以及gp120特异性细胞免疫。