Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial.
Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial.
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DOI：
10.1016/s2352-3018(21)00103-x
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发表时间：
2021-08
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通讯作者：
Oxford COVID Vaccine Trial Group
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作者：
Frater J;Ewer KJ;Ogbe A;Pace M;Adele S;Adland E;Alagaratnam J;Aley PK;Ali M;Ansari MA;Bara A;Bittaye M;Broadhead S;Brown A;Brown H;Cappuccini F;Cooney E;Dejnirattisai W;Dold C;Fairhead C;Fok H;Folegatti PM;Fowler J;Gibbs C;Goodman AL;Jenkin D;Jones M;Makinson R;Marchevsky NG;Mujadidi YF;Nguyen H;Parolini L;Petersen C;Plested E;Pollock KM;Ramasamy MN;Rhead S;Robinson H;Robinson N;Rongkard P;Ryan F;Serrano S;Tipoe T;Voysey M;Waters A;Zacharopoulou P;Barnes E;Dunachie S;Goulder P;Klenerman P;Screaton GR;Winston A;Hill AVS;Gilbert SC;Pollard AJ;Fidler S;Fox J;Lambe T;Oxford COVID Vaccine Trial Group
全球4000万艾滋病毒感染者需要关于SARS-CoV-2疫苗免疫原性的数据，这些人的功能性免疫力可能低于普通人群，相关的合并症可能更多。我们的目的是探索ChAdOx 1 nCoV-19（AZD 1222）疫苗在HIV感染者中的安全性和免疫原性。在大型II/III期试验COV 002方案中的这项单组开放标签疫苗接种子研究中，在英国伦敦的两家HIV诊所入组了18-55岁的成人HIV感染者。符合条件的参与者需要接受抗逆转录病毒治疗（ART），血浆HIV病毒载量不可检测（<50拷贝/mL），CD 4计数超过350个细胞/μL。ChAdOx 1 nCoV-19的初免-加强方案，两次给药间隔4-6周。该子研究的主要结局是疫苗的安全性和反应原性，由严重不良事件和征集性局部和全身反应确定。通过抗加标IgG ELISA和抗体介导的活病毒中和测定体液应答。通过体外IFN-γ酶联免疫斑点试验（ELISpot）和T细胞增殖来测量细胞介导的免疫应答。将所有结局与相同年龄组和给药策略的主要COV 002研究中的HIV未感染组进行比较，并报告至初次接种后第56天。在接受两种剂量和可用样本的所有参与者中分析结果。COV 002研究在ClinicalTrials.gov注册，NCT 04400838，目前正在进行中。在2020年11月5日至11月24日期间，54名HIV受试者（均为男性，中位年龄42.5岁[IQR 37.2 - 49.8]）入组并接受了两剂ChAdOx 1 nCoV-19。入组时的中位CD 4计数为694·0个细胞/μL（IQR 573·5-859·5）。未发生严重不良事件。初免后前7天内发生的局部和全身反应包括注射部位疼痛（53名参与者中有26名[49%]有可用数据），疲劳（25 [47%]），头痛（25 [47%]），不适（18 [34%]），寒战（12 [23%]），肌肉疼痛（19 [36%]），关节疼痛（5 [9%]）和恶心（4 [8%]），其频率与HIV阴性参与者相似。ELISA法测定的抗加标IgG应答在第42天达到峰值（中位数1440个ELISA单位[EU; IQR 704-2728]; n=50），并持续至第56天（中位数941个EU [531-1445]; n=49）。我们发现第56天抗峰IgG应答的幅度与CD 4细胞计数（p= 0.93）或年龄（p= 0.48）之间无相关性。ELISpot和T细胞增殖反应在初次给药后第14天和第28天达到峰值，并持续至第56天。与未感染HIV的受试者相比，我们发现SARS-CoV-2特异性体液或细胞反应的强度或持续性没有差异（所有分析p> 0.05）。在这项对HIV感染者的研究中，ChAdOx 1 nCoV-19是安全的和免疫原性的，支持对ART控制良好的人进行疫苗接种。英国研究与创新，美国国立卫生研究院（NIHR），流行病准备创新联盟，NIHR牛津生物医学研究中心，泰晤士河谷和南米德兰的NIHR临床研究网络，以及阿斯利康。
Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per μL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4–6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing. Between Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2–49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per μL (IQR 573·5–859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (26 [49%] of 53 participants with available data), fatigue (25 [47%]), headache (25 [47%]), malaise (18 [34%]), chills (12 [23%]), muscle ache (19 [36%]), joint pain (five [9%]), and nausea (four [8%]), the frequencies of which were similar to the HIV-negative participants. Anti-spike IgG responses by ELISA peaked at day 42 (median 1440 ELISA units [EUs; IQR 704–2728]; n=50) and were sustained until day 56 (median 941 EUs [531–1445]; n=49). We found no correlation between the magnitude of the anti-spike IgG response at day 56 and CD4 cell count (p=0·93) or age (p=0·48). ELISpot and T-cell proliferative responses peaked at day 14 and 28 after prime dose and were sustained to day 56. Compared with participants without HIV, we found no difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (p>0·05 for all analyses). In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.