Vaccine efficacy of NVX-CoV2373 against SARS-CoV-2 infection in adolescents in the USA: an ancillary study to a phase 3, observer-blinded, randomised, placebo-controlled trial

IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES
Meagan E Deming MD PhD , Prof Elizabeth R Brown ScD , Monica A McArthur MD PhD , Stephanie J Schrag DPhil , Melissa Arvay PhD , Mike Humphrys MS , Prof Jacques Ravel PhD , Jeffrey Adelglass MD , Brandon Essink MD , David B Musante MD , Rebecca Maguire MPH , Richard Gorman MD , Elizabeth Formentini MSN MBA , Robin Mason MS MBA , Merlin L Robb MD , Prof Kathleen M Neuzil MD MPH , Rekha R Rapaka MD PhD , Peter Wolff MHA , Prof Karen L Kotloff MD , Michael Waters
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We aimed to estimate the efficacy of the NVX-CoV2373 protein subunit vaccine against SARS-CoV-2 infection, regardless of symptoms, among adolescents.</div></div><div><h3>Methods</h3><div>We performed an ancillary observational study (SNIFF) to the phase 3, observer-blinded, randomised, placebo-controlled PREVENT-19 trial that assessed vaccine efficacy against symptomatic COVID-19 in the USA. Participants in the PREVENT-19 trial included healthy adolescents aged 12–17 years and with no history of laboratory-confirmed SARS-CoV-2 infection. They were randomly assigned (2:1) to receive either the NVX-CoV2373 (Novavax, Gaithersburg, MD, USA) vaccine (immediate NVX-CoV2373 group) or placebo (delayed NVX-CoV2373 group) on days 0 and 21 (initial series). After 2 months, in a crossover series, participants received two doses, 21 days apart, of the intervention that they did not receive in their initial series. Participants at 47 of the PREVENT-19 sites were invited to participate in the SNIFF study and self-collect nasal swabs at home twice weekly for SARS-CoV-2 testing to assess vaccine efficacy against SARS-CoV-2 infection. This primary outcome was defined as the first identification of SARS-CoV-2 detected by RT-PCR, regardless of symptoms, with onset within 4 weeks after the second dose of the initial vaccination series until the second dose of the crossover series. Secondary outcomes were vaccine efficacy against asymptomatic and minimally symptomatic SARS-CoV-2 infection, durability of vaccine efficacy against SARS-CoV-2 infection, and durability of vaccine efficacy against asymptomatic and minimally symptomatic infections. Outcomes were analysed in the modified intention-to-treat population, which included all participants without previous SARS-CoV-2 infection and was restricted to participants enrolled within 4 weeks of the second dose of the primary (primary analysis population) or crossover (post-crossover analysis population) series. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT04611802</span><svg><path></path></svg></span>).</div></div><div><h3>Findings</h3><div>Between June 1 and Dec 17, 2021, 1196 (53·2%) of the 2247 adolescent participants recruited in the PREVENT-19 trial enrolled in the SNIFF study. The primary analysis population included 471 participants in the immediate NVX-CoV2373 group and 220 in the delayed NVX-CoV2373 group. 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引用次数: 0

Abstract

Background

Although existing COVID-19 vaccines are known to be highly effective against severe disease and death, data are needed to assess their ability to reduce SARS-CoV-2 infection. We aimed to estimate the efficacy of the NVX-CoV2373 protein subunit vaccine against SARS-CoV-2 infection, regardless of symptoms, among adolescents.

Methods

We performed an ancillary observational study (SNIFF) to the phase 3, observer-blinded, randomised, placebo-controlled PREVENT-19 trial that assessed vaccine efficacy against symptomatic COVID-19 in the USA. Participants in the PREVENT-19 trial included healthy adolescents aged 12–17 years and with no history of laboratory-confirmed SARS-CoV-2 infection. They were randomly assigned (2:1) to receive either the NVX-CoV2373 (Novavax, Gaithersburg, MD, USA) vaccine (immediate NVX-CoV2373 group) or placebo (delayed NVX-CoV2373 group) on days 0 and 21 (initial series). After 2 months, in a crossover series, participants received two doses, 21 days apart, of the intervention that they did not receive in their initial series. Participants at 47 of the PREVENT-19 sites were invited to participate in the SNIFF study and self-collect nasal swabs at home twice weekly for SARS-CoV-2 testing to assess vaccine efficacy against SARS-CoV-2 infection. This primary outcome was defined as the first identification of SARS-CoV-2 detected by RT-PCR, regardless of symptoms, with onset within 4 weeks after the second dose of the initial vaccination series until the second dose of the crossover series. Secondary outcomes were vaccine efficacy against asymptomatic and minimally symptomatic SARS-CoV-2 infection, durability of vaccine efficacy against SARS-CoV-2 infection, and durability of vaccine efficacy against asymptomatic and minimally symptomatic infections. Outcomes were analysed in the modified intention-to-treat population, which included all participants without previous SARS-CoV-2 infection and was restricted to participants enrolled within 4 weeks of the second dose of the primary (primary analysis population) or crossover (post-crossover analysis population) series. This study is registered with ClinicalTrials.gov (NCT04611802).

Findings

Between June 1 and Dec 17, 2021, 1196 (53·2%) of the 2247 adolescent participants recruited in the PREVENT-19 trial enrolled in the SNIFF study. The primary analysis population included 471 participants in the immediate NVX-CoV2373 group and 220 in the delayed NVX-CoV2373 group. Incidence of SARS-CoV-2 infection was 14·9 cases per 100 person-years (95% CI 7·9–25·5) in the immediate group and 54·2 cases per 100 person-years (33·6–82·9) in the delayed group; vaccine efficacy was 73·5% (95% CI 47·1–86·7; p=0·0002). Incidence of minimally symptomatic or asymptomatic SARS-CoV-2 infection was 10·3 cases per 100 person-years (95% CI 4·7–19·6) in the immediate group and 36·1 cases per 100 person-years (19·8–60·7) in the delayed group; vaccine efficacy was 72·8% (95% CI 37·1–88·2; p=0·0023). After the second crossover dose, incidence of SARS-CoV-2 was 14·6 cases per 100 person-years (95% CI 8·6–23·0) in the immediate group (receiving placebo at crossover) and 9·1 cases per 100 person-years (3·0–21·3) in the delayed group, with a durability ratio of 160·3 (95% CI 59·5–431·6; p=0·35). Almost all infections after crossover were minimally symptomatic or asymptomatic, with a durability ratio of 151·4 (55·9–410·4; p=0·41).

Interpretation

Among adolescents participating in the PREVENT-19 trial during the delta (B.1.617.2) variant wave of the COVID-19 pandemic, the NVX-CoV2373 vaccine was highly efficacious against SARS-CoV-2 infection regardless of symptoms, indicating its potential to reduce the reservoir of infections that contribute to community transmission.

Funding

US Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, National Institute of Allergy and Infectious Diseases, and National Institutes of Health.
NVX-CoV2373 疫苗对美国青少年 SARS-CoV-2 感染的疗效:一项第 3 期观察盲法随机安慰剂对照试验的辅助研究。
背景:虽然已知现有的COVID-19疫苗对严重疾病和死亡非常有效,但需要数据来评估其减少SARS-CoV-2感染的能力。我们的目的是评估NVX-CoV2373蛋白亚单位疫苗在青少年中抗SARS-CoV-2感染的有效性,无论症状如何。方法:我们对在美国进行的3期、观察者盲、随机、安慰剂对照的prevention -19试验进行了一项辅助观察性研究(SNIFF),该试验评估了疫苗对症状性COVID-19的疗效。prevention -19试验的参与者包括12-17岁的健康青少年,没有实验室确诊的SARS-CoV-2感染史。他们被随机分配(2:1)在第0天和第21天(初始系列)接受NVX-CoV2373 (Novavax, Gaithersburg, MD, USA)疫苗(立即NVX-CoV2373组)或安慰剂(延迟NVX-CoV2373组)。2个月后,在交叉系列中,参与者接受了两剂干预,间隔21天,他们在最初的系列中没有接受干预。47个prevention -19站点的参与者被邀请参加了SNIFF研究,并每周两次在家中自行收集鼻拭子进行SARS-CoV-2检测,以评估疫苗对SARS-CoV-2感染的有效性。这一主要结局被定义为首次通过RT-PCR检测到SARS-CoV-2,无论症状如何,且在初始疫苗接种系列第二剂至交叉系列第二剂后4周内发病。次要结局是疫苗对无症状和轻微症状SARS-CoV-2感染的疗效、疫苗对SARS-CoV-2感染的疗效持久性、疫苗对无症状和轻微症状感染的疗效持久性。结果在修改意向治疗人群中进行分析,其中包括所有先前没有SARS-CoV-2感染的参与者,并且仅限于在第二次剂量(主要分析人群)或交叉(交叉后分析人群)系列的4周内入组的参与者。本研究已在ClinicalTrials.gov注册(NCT04611802)。研究结果:在2021年6月1日至12月17日期间,在prevention -19试验中招募的2247名青少年参与者中,有1196名(53.2%)入组了嗅探研究。主要分析人群包括471名即刻NVX-CoV2373组参与者和220名延迟NVX-CoV2373组参与者。立即治疗组SARS-CoV-2感染发生率为14.9例/ 100人年(95% CI为7.9 ~ 25.5),延迟治疗组为54.2例/ 100人年(33.6 ~ 82.9);疫苗有效率为73.5% (95% CI为47.1 ~ 86.7;p = 0·0002)。立即治疗组最小症状或无症状SARS-CoV-2感染发生率为10.3例/ 100人年(95% CI为4.7 ~ 19.6),延迟治疗组为36.1例/ 100人年(95% CI为19.8 ~ 607);疫苗有效率为72.8% (95% CI为37.1 ~ 88.2;p = 0·0023)。在第二次交叉剂量后,立即治疗组(在交叉时接受安慰剂)的SARS-CoV-2发病率为每100人年14.6例(95% CI为8.6 - 23.0),延迟治疗组为每100人年9.1例(3.0 - 21.3),持久性比为160·3 (95% CI为59.5 - 431.6;p = 0·35)。交叉感染后几乎所有感染均为轻微症状或无症状,持久性比为151·4(55·9 ~ 410·4;p = 0·41)。解释:在COVID-19大流行delta (B.1.617.2)变异波期间参加prevention -19试验的青少年中,NVX-CoV2373疫苗对SARS-CoV-2感染无论症状如何都非常有效,表明其有可能减少导致社区传播的感染库。资助:美国卫生与公众服务部、战略准备和反应管理局、生物医学高级研究与开发局、国家过敏和传染病研究所以及国家卫生研究院。
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来源期刊
Lancet Microbe
Lancet Microbe Multiple-
CiteScore
27.20
自引率
0.80%
发文量
278
审稿时长
6 weeks
期刊介绍: The Lancet Microbe is a gold open access journal committed to publishing content relevant to clinical microbiologists worldwide, with a focus on studies that advance clinical understanding, challenge the status quo, and advocate change in health policy.
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