Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial.
Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial.
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DOI：
10.1016/s2352-3018(21)00157-0
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发表时间：
2021-09
期刊：
影响因子：
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通讯作者：
Wits VIDA COVID team
中科院分区：
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作者：
Madhi SA;Koen AL;Izu A;Fairlie L;Cutland CL;Baillie V;Padayachee SD;Dheda K;Barnabas SL;Bhorat QE;Briner C;Aley PK;Bhikha S;Hermanus T;Horne E;Jose A;Kgagudi P;Lambe T;Masenya M;Masilela M;Mkhize N;Moultrie A;Mukendi CK;Moyo-Gwete T;Nana AJ;Nzimande A;Patel F;Rhead S;Taoushanis C;Thombrayil A;van Eck S;Voysey M;Villafana TL;Vekemans J;Gilbert SC;Pollard AJ;Moore PL;Kwatra G;Wits VIDA COVID team
与艾滋病毒阴性个体相比，艾滋病毒感染者在因严重COVID-19入院时死亡的风险增加。我们旨在评估ChAdOx 1 nCoV-19（AZD 1222）疫苗在南非HIV感染者和HIV阴性个体中的安全性和免疫原性。在这项正在进行的双盲、安慰剂对照、1B/2A期试验（COV 005）中，年龄在18-65岁之间的HIV感染者和HIV阴性参与者在南非的7个地点入组，并在完全分配隐藏的情况下随机分配（1：1）接受ChAdOx 1 nCoV-19的初免-加强方案，两次剂量间隔28天。艾滋病毒感染者的资格标准包括接受抗逆转录病毒治疗至少3个月，血浆艾滋病毒载量低于1000拷贝/毫升。在这项中期分析中，评估了在入组至2021年1月15日期间接受至少一剂ChAdOx 1 nCov 19的所有个体的安全性和反应原性。主要免疫原性分析包括接受两剂试验干预药物且基线时SARS-CoV-2血清阴性的受试者。本试验已在ClinicalTrials.gov（NCT 04444674）和泛非临床试验注册中心（PACTR 202006922165132）注册。2020年6月24日至11月12日期间，104名艾滋病毒感染者和70名艾滋病毒阴性者入组。102名HIV感染者（52名疫苗; 50名安慰剂）和56名HIV阴性参与者（28名疫苗; 28名安慰剂）接受了启动剂量，100名HIV感染者（51名疫苗; 49名安慰剂）和46名HIV阴性参与者（24名疫苗; 22名安慰剂）接受了两剂（启动和加强）。在基线时SARS-CoV-2血清阴性的参与者中，HIV感染者发生了164起不良事件（86起疫苗; 78起安慰剂），HIV阴性参与者发生了237起不良事件（95起疫苗; 142起安慰剂）。在7例严重不良事件中，1例HIV阴性受试者的重度发热肯定与试验干预相关，1例HIV受试者的丙氨酸氨基转移酶严重升高不太可能相关;其他5例被认为不相关。一名艾滋病毒感染者死亡（不太可能相关）。HIV感染者和HIV阴性参与者显示出针对野生型Wuhan-1 Asp 614 Gly（也称为D 614 G）的疫苗诱导血清IgG应答。对于基线时SARS-CoV-2抗原血清阴性的参与者，第28天的全长峰值几何平均浓度（GMC）为163·7结合抗体单位（BAU）/mL HIV感染者（n=36）和112·3 BAU/mL（95% CI 89·9-298·1）（61.7 - 204.4），两组中第42天GMC增强反应均上升。基线SARS-CoV-2血清阳性的HIV感染者在每次接种疫苗后的抗体应答均高于基线血清阴性的HIV感染者。无论HIV状态如何，均观察到β变体（B.1.351）全长刺突和受体结合结构域的高水平结合抗体交叉反应性。在产生高滴度应答的HIV感染者中，主要是入组时受体结合域血清阳性的HIV感染者，保留了对β的中和活性。ChAdOx 1 nCoV-19耐受性良好，在HIV感染者中显示出良好的安全性和免疫原性，包括在SARS-CoV-2基线血清阳性参与者中的免疫原性增强。HIV感染者对β变体和Asp 614 Gly野生型表现出交叉反应性结合抗体，高应答者保留了对β的中和作用。比尔和梅林达盖茨基金会，南非医学研究理事会，英国研究和创新，英国国家卫生研究所，南非医学研究理事会。
People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa. In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18–65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9–298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7–204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. In people with HIV who developed high titre responses, predominantly those who were receptor-binding domain seropositive at enrolment, neutralising activity against beta was retained. ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta. The Bill & Melinda Gates Foundation, South African Medical Research Council, UK Research and Innovation, UK National Institute for Health Research, and the South African Medical Research Council.