Deming Meagan E, Brown Elizabeth R, McArthur Monica A, Schrag Stephanie J, Arvay Melissa, Humphrys Mike, Ravel Jacques, Adelglass Jeffrey, Essink Brandon, Musante David B, Maguire Rebecca, Gorman Richard, Formentini Elizabeth, Mason Robin, Robb Merlin L, Neuzil Kathleen M, Rapaka Rekha R, Wolff Peter, Kotloff Karen L
Biomedical Advanced Research and Development Authority, Washington, DC, USA.
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lancet Microbe. 2025 Apr;6(4):100984. doi: 10.1016/j.lanmic.2024.100984. Epub 2025 Jan 27.
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.
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).
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).
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.
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.
尽管已知现有的新冠病毒疫苗对重症疾病和死亡具有高度有效性，但仍需要数据来评估其降低严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的能力。我们旨在评估NVX-CoV2373蛋白亚单位疫苗在青少年中预防SARS-CoV-2感染（无论有无症状）的有效性。
我们对一项3期、观察者盲法、随机、安慰剂对照的PREVENT-19试验进行了一项辅助观察性研究（SNIFF），该试验在美国评估了疫苗对有症状新冠病毒病（COVID-19）的有效性。PREVENT-19试验的参与者包括12至17岁的健康青少年，且无实验室确诊的SARS-CoV-2感染史。他们在第0天和第21天被随机分配（2:1）接受NVX-CoV2373（诺瓦瓦克斯公司，美国马里兰州盖瑟斯堡）疫苗（即时NVX-CoV2373组）或安慰剂（延迟NVX-CoV2373组）（初始系列）。2个月后，在交叉系列中，参与者接受两剂间隔21天的干预措施，这是他们在初始系列中未接受的。PREVENT-19试验中47个地点的参与者被邀请参加SNIFF研究，并在家中每周两次自行采集鼻拭子进行SARS-CoV-2检测以评估疫苗对SARS-CoV-2感染的有效性。主要结局定义为在初始疫苗接种系列的第二剂后至交叉系列的第二剂后4周内，通过逆转录聚合酶链反应（RT-PCR）首次检测到的SARS-CoV-2，无论有无症状。次要结局包括疫苗对无症状和症状轻微的SARS-CoV-2感染的有效性、疫苗对SARS-CoV-2感染有效性的持久性，以及疫苗对无症状和症状轻微感染有效性的持久性。在改良意向性治疗人群中分析结局，该人群包括所有既往无SARS-CoV-2感染的参与者，并限于在主要（主要分析人群）或交叉（交叉后分析人群）系列的第二剂后4周内入组的参与者。本研究已在ClinicalTrials.gov注册（NCT04611802）。
2021年6月1日至12月17日，PREVENT-19试验招募的2247名青少年参与者中有1196名（53.2%）参加了SNIFF研究。主要分析人群包括即时NVX-CoV2373组的471名参与者和延迟NVX-CoV2373组的220名参与者。即时组SARS-CoV-2感染发病率为每100人年14.9例（95%置信区间7.9 - 25.5），延迟组为每100人年54.2例（33.6 - 82.9）；疫苗有效性为73.5%（95%置信区间47.1 - 86.7；p = 0.0002）。症状轻微或无症状的SARS-CoV-2感染发病率在即时组为每100人年10.3例（95%置信区间4.7 - 19.6），在延迟组为每100人年36.1例（19.8 - 60.7）；疫苗有效性为72.8%（95%置信区间37.1 - 88.2；p = 0.0023）。在第二次交叉剂量后，即时组（交叉时接受安慰剂）SARS-CoV-2发病率为每100人年14.6例（95%置信区间8.6 - 23.0），延迟组为每100人年9.1例（3.0 - 21.3），持久性比率为160.3（95%置信区间59.5 - 431.6；p = 0.35）。交叉后几乎所有感染症状轻微或无症状，持久性比率为151.4（55.9 - 410.4；p = 0.41）。
在新冠疫情德尔塔（B.1.617.2）变异株流行期间参与PREVENT-19试验的青少年中，NVX-CoV2373疫苗对SARS-CoV-2感染（无论有无症状）具有高度有效性，表明其有潜力减少有助于社区传播的感染源。
美国卫生与公众服务部、战略准备与应对管理局、生物医学高级研究与发展局、国家过敏和传染病研究所及美国国立卫生研究院。
