NVX-CoV2373 新冠疫苗对 B.1.351 变异株的有效性。
Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant.
机构信息
From Novavax, Gaithersburg, MD (V.S., L. Fries, S.C.-C., M.Z., C.B., G.A., E.F., J.S.P., A.R., S.N., I.C., G.M.G., F.D.); and the South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences (S.B., V.B., A.L.K., A.O.-J., A.T., S.A.M.), Wits Reproductive Health and HIV Institute (L. Fairlie, G.B.), University of the Witwatersrand, and Soweto Clinical Trials Centre (Q.B., A.E.B.), Johannesburg, Josha Research Centre, Bloemfontein (Z.H., J.J.L., S.F.), the Paediatric Infectious Diseases Unit (M.A., R.M.), the Respiratory and Critical Care Unit (U.L., N.L.), the Department of Obstetrics and Gynaecology (D.M.), Centre for the AIDS Programme of Research in South Africa (S.H.), and Kwazulu-Natal Research Innovation and Sequencing Platform (T.O.), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, the Setshaba Research Centre, Tshwane (M.S.L.M., A.P., K.A.), the Limpopo Clinical Research Initiative, Rustenburg (L. Fouche, P.-L.V.), the Madibeng Centre for Research, Department of Family Medicine, School of Health, University of Pretoria (C.L.), and the Aurum Institute (C.G.), Pretoria, the South African TB Vaccine Initiative (M.T., N.S., A.L.) and the Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine, and UCT Lung Institute (K.D., A.E.), University of Cape Town, and the Health Systems Research Unit and the HIV Prevention Research Unit, South African Medical Research Council (N.S., A.G.), Cape Town, Mzansi Ethical Research Centre, Middelburg (G.K., F.G.P.), and Peermed Clinical Trial Centre, Kempton Park (N.C.-G.) - all in South Africa.
出版信息
N Engl J Med. 2021 May 20;384(20):1899-1909. doi: 10.1056/NEJMoa2103055. Epub 2021 May 5.
BACKGROUND
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.
METHODS
In this phase 2a-b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)-negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection.
RESULTS
Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, -0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups.
CONCLUSIONS
The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.).
背景
严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）变体的出现威胁着控制 2019 年冠状病毒病（COVID-19）大流行的进展。在一项涉及健康成年人的 1-2 期试验中，NVX-CoV2373 纳米颗粒疫苗具有可接受的安全性，并与强大的中和抗体和抗原特异性多效性 CD4+T 细胞反应相关。需要在 SARS-CoV-2 持续传播的环境中评估疫苗的疗效。
方法
在南非的这项 2a-b 期试验中，我们将年龄在 18 至 84 岁之间的 HIV 阴性成年人或年龄在 18 至 64 岁之间且医学稳定的 HIV 阳性参与者以 1:1 的比例随机分配，接受两剂 NVX-CoV2373 疫苗（5μg 重组刺突蛋白和 50μg Matrix-M1 佐剂）或安慰剂。主要终点是在第二次接种后 7 天或以上，无 SARS-CoV-2 既往感染的参与者中，实验室确诊的有症状 COVID-19 的安全性和疫苗疗效。
结果
在接受筛选的 6324 名参与者中，有 4387 名接受了至少一剂疫苗或安慰剂。大约 30%的参与者在基线时对 SARS-CoV-2 呈血清阳性。在 2684 名基线血清阴性参与者（94% HIV 阴性和 6% HIV 阳性）中，疫苗组 15 名参与者和安慰剂组 29 名参与者出现了主要为轻度至中度 COVID-19（疫苗疗效，49.4%；95%置信区间 [CI]，6.1 至 72.8）。HIV 阴性参与者的疫苗疗效为 60.1%（95%CI，19.9 至 80.1）。在 41 个测序分离株中，38 个（92.7%）为 B.1.351 变体。在 HIV 阴性参与者中，针对 B.1.351 的事后疫苗疗效为 51.0%（95%CI，-0.6 至 76.2）。在疫苗组中更常见局部和全身反应性事件；两组均罕见严重不良事件。
结论
NVX-CoV2373 疫苗在预防 COVID-19 方面是有效的，在 HIV 阴性参与者中观察到更高的疫苗疗效。大多数感染是由 B.1.351 变体引起的。（由 Novavax 和比尔和梅琳达盖茨基金会资助；临床试验.gov 编号，NCT04533399）。
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