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. 2025 Jun 5:61:127362.
doi: 10.1016/j.vaccine.2025.127362. Online ahead of print.

Safety and immunogenicity of four sequential doses of NVX-CoV2373 in adults and adolescents: A phase 3, randomized, placebo-controlled trial (PREVENT-19)

Germán Áñez  1 , Alice McGarry  1 , Wayne Woo  1 , Karen L Kotloff  2 , Cynthia L Gay  3 , Mingzhu Zhu  1 , Shane Cloney-Clark  1 , Joy Nelson  1 , Haoua Dunbar  1 , Miranda R Cai  1 , Iksung Cho  1 , Zhaohui Cai  1 , Raj Kalkeri  1 , Joyce S Plested  1 , Nita Patel  1 , Katherine Smith  1 , Anthony M Marchese  1 , Gregory M Glenn  1 , Raburn M Mallory  1 , Lisa M Dunkle  4 ; 2019CoVn-301 Study Investigators
Affiliations

Safety and immunogenicity of four sequential doses of NVX-CoV2373 in adults and adolescents: A phase 3, randomized, placebo-controlled trial (PREVENT-19)

Germán Áñez et al. Vaccine. .

Abstract

Background: NVX-CoV2373, a recombinant SARS-CoV-2 spike (rS) protein vaccine with Matrix-M® adjuvant, has been authorized for use in adults and adolescents. PREVENT-19 (NCT04611802/2019nCoV-301), a pivotal phase 3, randomized, placebo-controlled trial demonstrated robust efficacy of a primary, 2-dose series of NVX-CoV2373 against COVID-19.

Methods: Protocol expansions to PREVENT-19 included enrollment of adolescents (aged 12 to <18 years) and administration of 3rd and 4th doses of NVX-CoV2373 to adults and adolescents. Participants randomized 2:1 received NVX-CoV2373 or placebo 21 days apart; 3rd and 4th doses were administered ≥6 months after the preceding dose. Secondary and additional assessments included post-3rd- and 4th-dose immune responses (neutralizing antibody [nAb], anti-rS IgG, human angiotensin-converting enzyme-2-receptor binding inhibition [hACE2-RBI]) and response durability (post-3rd dose) to ancestral virus; cross-reactivity to Omicron subvariants; safety; and reactogenicity.

Results: Immune responses were observed against ancestral virus after two doses of NVX-CoV2373 but not after placebo. In both adults and adolescents, additional doses of NVX-CoV2373 increased nAb titers, anti-rS IgG levels, and hACE2-RBI; durable responses were recorded 8 months post 3rd dose. nAb responses post 3rd dose were noninferior to those post primary series. Cross-reactivity to BA.5 and BQ.1.1 variants was also observed, with anti-rS IgG levels post 3rd or 4th dose exceeding previously reported correlates of protection. Additional doses of NVX-CoV2373 were well tolerated, with no new safety signals.

Conclusions: NVX-CoV2373 elicited robust and durable humoral immune responses to ancestral SARS-CoV-2 as a 3rd and 4th dose after the primary series in adults and adolescents. Cross-reactivity to relevant variants provides insight into potential protection against antigenically related, but shifted, viral strains. Additional doses of NVX-CoV2373 were well tolerated with no new safety signals. These results support the utility of this vaccine platform and continued updates, based on currently circulating strains, to help effectively combat SARS-CoV-2 infection.

Keywords: Adolescent; Booster; COVID-19; Durability; Reactogenicity; Vaccine.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: Karen L. Kotloff reports financial support was provided by Novavax, Inc. and the National Institute of Allergy and Infectious Diseases. Cynthia L. Gay reports financial support was provided by National Institute of Allergy and Infectious Diseases. Alice McGarry, Wayne Woo, Mingzhu Zhu, Shane Cloney-Clark, Joy Nelson, Haoua Dunbar, Miranda R. Cai, Iksung Cho, Zhaohui Cai, Raj Kalkeri, Joyce S. Plested, Nita Patel, Katherine Smith, Anthony M. Marchese, and Raburn M. Mallory report a relationship with Novavax, Inc. that includes: employment and equity or stocks. German Anez reports a relationship with Novavax, Inc. that includes: employment (former) and equity or stocks. Gregory Glenn reports a relationship with Novavax, Inc. that includes: consulting or advisory, employment (former), and equity or stocks. Lisa Dunkle reports a relationship with Novavax, Inc. that includes: consulting or advisory, employment (former), and equity or stocks. Karen L. Kotloff reports a relationship with Novavax, Inc. that includes: funding grants. Medical writing support was funded by Novavax, Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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References

    1. COVID-19 Vaccine Tracker. Novavax: Nuvaxovid https://covid19.trackvaccines.org/vaccines/25/. Accessed January 16, 2024.
    1. Food and Drug Administration. Novavax COVID-19 Vaccine, Adjuvanted. Available online 17 October 2023. https://www.fda.gov/vaccines-blood-biologics/coronavirus-covid-19-cber-r.... Accessed January 31, 2024.
    1. European Medicines Agency. Nuvaxovid. COVID-19 Vaccine (recombinant, adjuvanted). https://www.ema.europa.eu/en/medicines/human/EPAR/nuvaxovid#ema-inpage-i.... Accessed February 1, 2024.
    1. World Health Organization. Updated Risk Evaluation of JN.1, 15 April 2024. https://www.who.int/docs/default-source/coronaviruse/15042024_jn1_ure.pd.... Accessed May 13, 2024.
    1. Link-Gelles R, Ciesla AA, Mak J, et al. Early Estimates of Updated 2023–2024 (Monovalent XBB.1.5) COVID-19 Vaccine Effectiveness Against Symptomatic SARS-CoV-2 Infection Attributable to Co-Circulating Omicron Variants Among Immunocompetent Adults - Increasing Community Access to Testing Program, United States, September 2023-January 2024. MMWR Morb Mortal Wkly Rep. 2024;73(4):77–83. - PMC - PubMed

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