Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Apr 3;6(4):e239135.
doi: 10.1001/jamanetworkopen.2023.9135.

Safety, Immunogenicity, and Efficacy of the NVX-CoV2373 COVID-19 Vaccine in Adolescents: A Randomized Clinical Trial

Germán Áñez  1   2 , Lisa M Dunkle  1 , Cynthia L Gay  3 , Karen L Kotloff  4 , Jeffrey M Adelglass  5 , Brandon Essink  6 , James D Campbell  4 , Shane Cloney-Clark  1 , Mingzhu Zhu  1 , Joyce S Plested  1 , Pavitra Roychoudhury  7 , Alexander L Greninger  7 , Nita Patel  1 , Alice McGarry  1 , Wayne Woo  1 , Iksung Cho  1 , Gregory M Glenn  1 , Filip Dubovsky  1 ; 2019nCoV-301–Pediatric Expansion Study Group
Collaborators, Affiliations
Clinical Trial

Safety, Immunogenicity, and Efficacy of the NVX-CoV2373 COVID-19 Vaccine in Adolescents: A Randomized Clinical Trial

Germán Áñez et al. JAMA Netw Open. .

Abstract

Importance: Greater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents.

Objective: To evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents.

Design, setting, and participants: The NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized.

Interventions: Participants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.

Main outcomes and measures: Serologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18-25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety.

Results: Among 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57-69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31-6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%-92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%-95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation.

Conclusions and relevance: The findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents.

Trial registration: ClinicalTrials.gov Identifier: NCT04611802.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Gay reported receiving grant funding from University of North Carolina at Chapel Hill during the conduct of the study and grant funding for her institution from the US National Institute of Allergy and Infectious Diseases (NIAID). Dr Kotloff reported receiving grant funding from the National Institutes of Health (NIH) during the conduct of the study. Dr Campbell reported receiving grant funding from the NIH during the conduct of the study and from Sanofi SA, Merck & Co, Inc, Pfizer Inc, Moderna, Inc, and GlaxoSmithKline outside the submitted work; payments to his institution to perform this study from the NIAID, NIH; and serving as an unpaid vice chair on the Committee on Infectious Diseases for the American Academy of Pediatrics. Drs Áñez, Dunkle, Zhu, Plested, Glenn, and Dubovky, Ms Cloney-Clark, Patel, and McGarry, and Mssrs Woo and Cho reported being stockholders in Novavax, Inc outside and inclusive of the submitted work. Dr Roychoudhury reported receiving speaking fees from the Gates Discovery Center and the Association for Molecular Pathology outside the submitted work and a testing contract to her institution from Novavax, Inc, Janssen Pharmaceuticals, and Pfizer Inc. Dr Greninger reported a testing contract to his institution from Novavax, Inc, during the conduct of the study; receiving grant funding from Gilead Sciences, Inc, outside the submitted work; and performing contract testing for Abbott Laboratories, Cepheid, Pfizer Inc, Janssen Pharmaceuticals, and Hologic, Inc, outside of the described work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Trial Disposition
The full analysis set (FAS) included all participants who were randomly assigned to treatment and received at least 1 dose, regardless of protocol violations or missing data, and are analyzed according to the trial vaccine group as randomized. ITT indicates intention to treat; NP, nucleoprotein; and RT-PCR, reverse transcriptase–polymerase chain reaction. aParticipants could have more than 1 reason for exclusion.
Figure 2.
Figure 2.. Solicited Local and Systemic Adverse Events
The percentage of participants in each treatment group with solicited local (A) and systemic (B) adverse events during the 7 days after each vaccination is plotted by US Food and Drug Administration toxicity grade, as any (mild, moderate, severe, or potentially life-threatening) or as grade 3 or higher (severe or potentially life-threatening).
Figure 3.
Figure 3.. Cumulative Incidence Plot of Overall Efficacy of NVX-CoV2373 Against Symptomatic COVID-19
Prospective surveillance of COVID-19 illness in the full analysis population started from the first dose of NVX-CoV2373 or placebo. The per-protocol symptomatic COVID-19 cases were defined as beginning at least 7 days after the second dose (ie, day 28) through approximately 3 to 4 months of follow-up (the implementation of blinded crossover), unblinding or receipt of emergency use authorization vaccine. MDI indicates mean disease incidence; PY, person-years; and VE, vaccine efficacy.
See this image and copyright information in PMC

References

    1. US Centers for Disease Control and Prevention . Why children and teens should get vaccinated against COVID-19. Updated December 22, 2022. Accessed November 1, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/why-vaccinate-childre...
    1. US Centers for Disease Control and Prevention . COVID-19 vaccine recommendations for children and teens. Updated March 2, 2023. Accessed November 1, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/vaccines-children-tee...
    1. Novavax. First quarter 2022 financial results & operational highlights. May 9, 2022. Accessed November 1, 2022. https://novavax.widen.net/s/zlznqr9b8r/1q22-earnings-slides-final
    1. World Health Organization . COVID-19 vaccines with WHO emergency use listing. Updated May 19, 2022. Accessed November 1, 2022. https://extranet.who.int/pqweb/vaccines/vaccinescovid-19-vaccine-eul-issued
    1. Novavax. Novavax and Serum Institute of India announce first emergency use authorization of Novavax’ COVID-19 vaccine in adolescents ≥12 to <18 in India. March 22, 2022. Accessed November 1, 2022. https://ir.novavax.com/2022-03-22-Novavax-and-Serum-Institute-of-India-A...

Publication types

Substances

Supplementary concepts

Associated data