Immunogenicity and safety of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine in people living with and without HIV-1 infection: a randomised, controlled, phase 2A/2B trial,The Lancet HIV

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Immunogenicity and safety of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine in people living with and without HIV-1 infection: a randomised, controlled, phase 2A/2B trial
The Lancet HIV ( IF 12.8 ) Pub Date : 2022-04-27 , DOI: 10.1016/s2352-3018(22)00041-8
Shabir A Madhi ₁ , Dhayendre Moodley ₂ , Sherika Hanley ₃ , Moherndran Archary ₄ , Zaheer Hoosain ₅ , Umesh Lalloo ₆ , Cheryl Louw ₇ , Lee Fairlie ₈ , Leon Frederik Fouche ₉ , Mduduzi S L Masilela ₁₀ , Nishanta Singh ₁₁ , Coert Grobbelaar ₁₂ , Khatija Ahmed ₁₃ , Gabriella Benadé ₈ , Sutika Bhikha ₁₄ , As'ad Ebrahim Bhorat ₁₅ , Qasim Bhorat ₁₅ , Natasha Joseph ₁₆ , Keertan Dheda ₁₇ , Aliasgar Esmail ₁₈ , Sharne Foulkes ₅ , Ameena Goga ₁₉ , Aylin Oommen Jose ₁₄ , Gertruida Kruger ₂₀ , Dishiki J Kalonji ₂₁ , Natasha Lalloo ₆ , Johan J Lombaard ₅ , Anthonet Lombard Koen ₁₄ , Angelique Kany Luabeya ₁₁ , Rosie Mngqibisa ₄ , Friedrich G Petrick ₂₀ , Annah Pitsi ₁₀ , Michele Tameris ₁₁ , Asha Thombrayil ₁₄ , Pieter-Louis Vollgraaff ₉ , Shane Cloney-Clark ₂₂ , Mingzhu Zhu ₂₂ , Chijioke Bennett ₂₂ , Gary Albert ₂₂ , Emmanuel Faust ₂₂ , Joyce S Plested ₂₂ , Lou Fries ₂₂ , Andreana Robertson ₂₂ , Susan Neal ₂₂ , Iksung Cho ₂₂ , Greg M Glenn ₂₂ , Vivek Shinde ₂₂ ,

Affiliation

Vaccines and Infectious Diseases Analytics Research Unit, South African Medical Research Council, University of the Witwatersrand, Johannesburg, South Africa; African Leadership in Vaccinology Expertise, University of the Witwatersrand, Johannesburg, South Africa.
Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, Durban, South Africa.
Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
Enhancing Care Foundation, Durban, South Africa.
Josha Research Centre, Bloemfontein, South Africa.
Respiratory and Critical Care Unit, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Madibeng Centre for Research, Department of Family Medicine, University of Pretoria, Pretoria, South Africa.
Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa.
Limpopo Clinical Research Initiative, Thabazimbi, South Africa.
Setshaba Research Centre, Tshwane, South Africa.
HIV Prevention Research Unit, South African Medical Research Council, Verulam and Isipingo Clinical Research Site, Durban, South Africa.
Aurum Institute, University of Pretoria, Pretoria, South Africa.
Department of Microbiology, University of Pretoria, Pretoria, South Africa; Setshaba Research Centre, Tshwane, South Africa.
Vaccines and Infectious Diseases Analytics Research Unit, South African Medical Research Council, University of the Witwatersrand, Johannesburg, South Africa.
Soweto Clinical Trials Centre, Johannesburg, South Africa.
MERC Research, Kempton Park, South Africa.
Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa; Faculty of Infectious and Tropical Diseases, Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK.
Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa.
Health Systems Research Unit and HIV Prevention Research Unit, South African Medical Research Council, Cape Town, South Africa.
MERC Research, Middelburg, South Africa.
HIV Prevention Research Unit, South Africa Medical Research Council, Isipingo, South Africa.
Novavax, Gaithersburg, MD, USA.

Background

There is a paucity of data on COVID-19 vaccines in people living with HIV-1, who could be at increased risk of severe illness and death from COVID-19. We evaluated the safety and immunogenicity of a Matrix-M adjuvanted recombinant spike protein nanoparticle COVID-19 vaccine (NVX-CoV2373; Novavax) in HIV-negative people and people living with HIV-1.

Methods

In this randomised, observer-blinded, multicentre, placebo-controlled phase 2A/B trial in South Africa, participants aged 18–84 years, with and without underlying HIV-1, were enrolled from 16 sites and randomly assigned (1:1) to receive two intramuscular injections of NVX-CoV2373 or placebo, 21 days apart. People living with HIV-1 were on stable antiretroviral therapy and had an HIV-1 viral load of less than 1000 copies per mL. Vaccine dosage was 5 μg SARS-CoV-2 recombinant spike protein with 50 μg Matrix-M adjuvant, whereas 0·9% saline was used as placebo injection (volume 0·5 mL each). All study staff and participants remained masked to study group assignment. We previously reported an interim analysis on the efficacy and safety of the NVX-CoV2373 vaccine (coprimary endpoints). In this Article, we present an expanded safety analysis for the full cohort of participants and report on the secondary objective of vaccine immunogenicity in the full cohort of people living with HIV-1 and in HIV-negative individuals overall and stratified by baseline SARS-CoV-2 serostatus. This trial is registered with ClinicalTrials.gov, NCT04533399, and the Pan-African Clinical Trials Registry, PACTR202009726132275.

Findings

Participants were enrolled between Aug 17 and Nov 25, 2020. The safety analysis set included 4164 HIV-negative participants (2089 in the intervention group and 2075 in the placebo group) and 244 people living with HIV-1 (122 in the intervention group and 122 in the placebo group). 1422 (34·1%) of 4164 HIV-negative people and 83 (34·0%) of 244 people living with HIV-1 were categorised as baseline SARS-CoV-2-positive (ie, anti-spike IgG reactive at enrolment or had a reactive SARS-CoV-2 nucleic acid amplification test by 14 days after the second study vaccination). In the NVX-CoV2373 group, solicited local and systemic adverse events were more common in HIV-negative participants (427 [30·6%] local and 401 [28·7%] systemic) than in people living with HIV-1 (20 [25·3%] local and 20 [25·3%] systemic) among those who were baseline SARS-CoV-2-seronegative (naive). Of the serious adverse events that occurred among HIV-negative people (of whom, two [0·1%] were baseline SARS-CoV-2-negative and four [0·6%] were baseline SARS-CoV-2-positive) and people living with HIV-1 (for whom there were no serious adverse events) in the NVX-CoV2373 group, none were assessed as related to the vaccine. Among participants who were baseline SARS-CoV-2-negative in the NVX-CoV2373 group, the anti-spike IgG geometric mean titres (GMTs) and seroconversion rates (SCRs) were lower in people living with HIV-1 (n=62) than in HIV-negative people (n=1234) following the first vaccination (GMT: 508·6 vs 1195·3 ELISA units [EU]/mL; SCR: 51·6% vs 81·3%); and similarly so 14 days after the second vaccination for GMTs (14 420·5 vs 31 631·8 EU/mL), whereas the SCR was similar at this point (100·0% vs 99·3%). In the NVX-CoV2373 group, anti-spike IgG GMTs 14 days after the second vaccination were substantially higher in those who were baseline SARS-CoV-2-positive than in those who were baseline SARS-CoV-2-seronegative for HIV-negative participants (100 666·1 vs 31 631·8 EU/mL) and for people living with HIV-1 (98 399·5 vs 14 420·5 EU/mL). This was also the case for angiotensin-converting enzyme 2 receptor-binding antibody and neutralising antibody titres.

Interpretation

The safety of the NVX-CoV2373 vaccine in people living with HIV-1 was similar to that in HIV-negative participants. However, people living with HIV-1 not previously exposed to SARS-CoV-2 had attenuated humoral immune responses to NVX-CoV2373 compared with their HIV-negative vaccine counterparts, but not so if they were baseline SARS-CoV-2-positive.

Funding

Novavax and the Bill & Melinda Gates Foundation; investigational vaccine manufacturing support was provided by the Coalition for Epidemic Preparedness Innovations.

中文翻译：

SARS-CoV-2 重组刺突蛋白纳米颗粒疫苗在感染和未感染 HIV-1 的人群中的免疫原性和安全性：一项随机、对照、2A/2B 期试验

背景

关于 HIV-1 感染者接种 COVID-19 疫苗的数据很少，这些人因 COVID-19 患严重疾病和死亡的风险可能会增加。我们评估了 Matrix-M 佐剂重组刺突蛋白纳米颗粒 COVID-19 疫苗（NVX-CoV2373；Novavax）在 HIV 阴性人群和 HIV-1 感染者中的安全性和免疫原性。

方法

在南非进行的这项随机、观察者盲法、多中心、安慰剂对照 2A/B 期试验中，年龄为 18-84 岁、患有或不患有潜在 HIV-1 的参与者从 16 个地点入组并随机分配（1:1）接受两次 NVX-CoV2373 或安慰剂肌肉注射，间隔 21 天。HIV-1 感染者正在接受稳定的抗逆转录病毒治疗，并且 HIV-1 病毒载量低于每毫升 1000 个拷贝。疫苗剂量为5 μg SARS-CoV-2重组刺突蛋白和50 μg Matrix-M佐剂，而0·9%盐水用作安慰剂注射液（每次体积0·5 mL）。所有研究人员和参与者均不知道研究小组的分配情况。我们之前报告了 NVX-CoV2373 疫苗功效和安全性的中期分析（共同主要终点）。在本文中，我们对整个参与者群体进行了扩展的安全性分析，并报告了整个 HIV-1 感染者和 HIV 阴性个体中疫苗免疫原性的次要目标，并按基线 SARS-CoV 进行了分层-2 血清状态。该试验已在 ClinicalTrials.gov（NCT04533399）和泛非临床试验注册中心（PACTR202009726132275）注册。

发现

参与者于 2020 年 8 月 17 日至 11 月 25 日期间入组。安全性分析集包括 4164 名 HIV 阴性参与者（干预组 2089 名，安慰剂组 2075 名）和 244 名 HIV-1 感染者（干预组 122 名，安慰剂组 122 名）。安慰剂组 122）。4164 名 HIV 阴性人群中的 1422 名 (34·1%) 和 244 名 HIV-1 感染者中的 83 名 (34·0%) 被归类为基线 SARS-CoV-2 阳性（即入组时抗尖峰 IgG 呈反应性）或在第二次研究疫苗接种后 14 天进行反应性 SARS-CoV-2 核酸扩增测试）。在 NVX-CoV2373 组中，与 HIV-1 感染者（20 [25·3%] 局部和 20 [25·3%] 全身）基线 SARS-CoV-2 血清阴性（未接触过）的患者。HIV 阴性人群中发生的严重不良事件（其中 2 例 [0·1%] 基线 SARS-CoV-2 阴性，4 例 [0·6%] 基线 SARS-CoV-2 阳性） NVX-CoV2373 组中的 HIV-1 感染者（没有出现严重不良事件），没有被评估为与疫苗相关。在 NVX-CoV2373 组中基线 SARS-CoV-2 阴性的参与者中，HIV-1 感染者的抗尖峰 IgG 几何平均滴度 (GMT) 和血清转化率 (SCR) 较低 (n=62)与首次接种疫苗后的 HIV 阴性人群 (n=1234) 相比（GMT：508·6 vs 1195·3 ELISA 单位 [EU]/mL；SCR：51·6% vs 81·3%）；第二次 GMT 疫苗接种后 14 天也是如此（14 420·5 vs 31 631·8 EU/mL），而此时 SCR 相似（100·0% vs 99·3%）。在 NVX-CoV2373 组中，第二次疫苗接种后 14 天，基线 SARS-CoV-2 阳性的患者的抗尖峰 IgG GMT 显着高于基线 SARS-CoV-2 血清阴性的患者（HIV 阴性）参与者（100 666·1 vs 31 631·8 EU/mL）和 HIV-1 感染者（98 399·5 vs 14 420·5 EU/mL）。血管紧张素转换酶 2 受体结合抗体和中和抗体滴度也是如此。

解释

NVX-CoV2373 疫苗对 HIV-1 感染者的安全性与 HIV 阴性参与者的安全性相似。然而，与 HIV 阴性疫苗接种者相比，之前未接触过 SARS-CoV-2 的 HIV-1 感染者对 NVX-CoV2373 的体液免疫反应减弱，但如果他们的基线 SARS-CoV-2 呈阳性，则情况并非如此。