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,The Lancet HIV

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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
The Lancet HIV ( IF 16.1 ) Pub Date : 2021-06-18 , DOI: 10.1016/s2352-3018(21)00103-x
John Frater ₁ , Katie J Ewer ₂ , Ane Ogbe ₃ , Mathew Pace ₃ , Sandra Adele ₃ , Emily Adland ₄ , Jasmini Alagaratnam ₅ , Parvinder K Aley ₆ , Mohammad Ali ₃ , M Azim Ansari ₃ , Anna Bara ₇ , Mustapha Bittaye ₂ , Samantha Broadhead ₈ , Anthony Brown ₃ , Helen Brown ₃ , Federica Cappuccini ₂ , Enya Cooney ₈ , Wanwisa Dejnirattisai ₉ , Christina Dold ₆ , Cassandra Fairhead ₈ , Henry Fok ₈ , Pedro M Folegatti ₂ , Jamie Fowler ₂ , Charlotte Gibbs ₈ , Anna L Goodman ₈ , Daniel Jenkin ₂ , Mathew Jones ₃ , Rebecca Makinson ₂ , Natalie G Marchevsky ₆ , Yama F Mujadidi ₆ , Hanna Nguyen ₈ , Lucia Parolini ₃ , Claire Petersen ₅ , Emma Plested ₆ , Katrina M Pollock ₇ , Maheshi N Ramasamy ₆ , Sarah Rhead ₆ , Hannah Robinson ₆ , Nicola Robinson ₁₀ , Patpong Rongkard ₃ , Fiona Ryan ₈ , Sonia Serrano ₁₁ , Timothy Tipoe ₃ , Merryn Voysey ₆ , Anele Waters ₈ , Panagiota Zacharopoulou ₃ , Eleanor Barnes ₁₂ , Susanna Dunachie ₁₃ , Philip Goulder ₁₄ , Paul Klenerman ₁ , Gavin R Screaton ₉ , Alan Winston ₅ , Adrian V S Hill ₂ , Sarah C Gilbert ₂ , Andrew J Pollard ₁₅ , Sarah Fidler ₅ , Julie Fox ₈ , Teresa Lambe ₂ ,

Affiliation

Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
The Jenner Institute, University of Oxford, Oxford, UK.
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK.
Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK; Department of HIV Medicine, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
Nuffield Department of Clinical Medicine and Oxford Vaccine Group, University of Oxford, Oxford, UK.
NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UK.
Department of Infection, Harrison Wing and NIHR Clinical Research Facility, Guys and St Thomas' NHS Trust, London, UK.
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
NIHR Guy's and St Thomas' Biomedical Research Centre, London, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; The Jenner Institute, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK.
Nuffield Department of Clinical Medicine and Oxford Vaccine Group, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.

Background

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.

Methods

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.

Findings

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).

Interpretation

In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART.

Funding

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.

中文翻译：

HIV 感染中针对 SARS-CoV-2 的 ChAdOx1 nCoV-19 (AZD1222) 疫苗的安全性和免疫原性：2/3 期临床试验的单臂亚研究

背景

全球 4000 万艾滋病毒感染者需要有关 SARS-CoV-2 疫苗免疫原性的数据，这些人的功能性免疫力可能比普通人群低，相关合并症也更多。我们的目的是探索 ChAdOx1 nCoV-19 (AZD1222) 疫苗在 HIV 感染者中的安全性和免疫原性。

方法

在这项更大的 2/3 期试验 COV002 方案范围内的单臂开放标签疫苗亚研究中，英国伦敦的两家 HIV 诊所招募了 18-55 岁的 HIV 感染者。符合条件的参与者必须接受抗逆转录病毒治疗 (ART)，且血浆 HIV 病毒载量无法检测到（<50 个拷贝/mL），且 CD4 计数超过每 μL 350 个细胞。ChAdOx1 nCoV-19 的初免-加强方案，分两次给药，间隔 4-6 周。该亚研究的主要结果是疫苗的安全性和反应原性，由严重不良事件和引起的局部和全身反应确定。通过抗尖峰 IgG ELISA 和抗体介导的活病毒中和来测量体液反应。通过离体 IFN-γ 酶联免疫斑点测定 (ELISpot) 和 T 细胞增殖来测量细胞介导的免疫反应。所有结果均与 COV002 主要研究中相同年龄组和剂量策略的未感染 HIV 组进行比较，并在初次疫苗接种后第 56 天进行报告。对接受两种剂量和可用样本的所有参与者的结果进行了分析。COV002 研究已在 ClinicalTrials.gov 注册（NCT04400838），并且正在进行中。

发现

2020 年 11 月 5 日至 24 日期间，54 名 HIV 感染者（均为男性，中位年龄 42·5 岁 [IQR 37·2–49·8]）入组并接受了两剂 ChAdOx1 nCoV-19。入组时 CD4 计数中位数为 694·0 个细胞/μL (IQR 573·5–859·5)。没有发生严重不良事件。初次疫苗接种后的前 7 天内发生的局部和全身反应包括注射部位疼痛（53 名有可用数据的参与者中的 26 名 [49%]）、疲劳（25 名 [47%]）、头痛（25 名 [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%]），其频率与艾滋病毒阴性参与者相似。ELISA 的抗尖峰 IgG 反应在第 42 天达到峰值（中位 1440 ELISA 单位 [EU；IQR 704–2728]；n=50），并持续到第 56 天（中位 941 EU[531-1445]；n=49）。我们发现第 56 天时抗尖峰 IgG 反应的强度与 CD4 细胞计数 (p=0·93) 或年龄 (p=0·48) 之间没有相关性。ELISpot 和 T 细胞增殖反应在初剂量后第 14 天和 28 天达到峰值，并持续到第 56 天。与未感染 HIV 的参与者相比，我们发现 SARS-CoV-2 尖峰特异性体液或细胞反应的强度或持久性没有差异（对于所有分析，p>0·05）。