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

Áñez, G., et al. Safety and immunogenicity of four sequential doses of NVX-CoV2373 in adults and adolescents: A phase 3, randomized, placebo-controlled trial (PREVENT-19). Vaccine, 2025 Jun 5, 61:127362. PMID: 40479932

• This study outlines the ongoing challenge posed by the SARS-CoV-2 virus and the importance of developing effective vaccines to combat COVID-19. It highlights the existing role of NVX-CoV2373, a recombinant spike protein vaccine with Matrix-M adjuvant (containing natural saponins), which has demonstrated robust efficacy and safety in previous trials, including those involving adolescents. The introduction emphasizes the need to evaluate the immunogenicity, durability, and safety of additional booster doses beyond the primary series (the 3rd and 4th doses) to understand their potential in maintaining protective immunity against circulating variants, including those with immune-evasive properties, such as Omicron. The study aims to expand the understanding of how these additional doses perform in both adults and adolescents in real-world applications.
• The results demonstrate that additional doses of NVX-CoV2373, administered as a 3rd and 4th dose, elicited robust and durable humoral immune responses against the ancestral SARS-CoV-2 strain in both adults and adolescents. These doses significantly increased neutralizing antibody titers, anti-spike IgG levels, and human ACE2 receptor-binding inhibition, with responses persisting up to 8 months post-vaccination. Cross-reactivity against variants of concern, such as BA.5 and BQ.1.1, was also observed, with antibody levels exceeding previously established correlates of protection. The study mentions that the broad cross-reactivity of the vaccine responses may be related to the properties of the platform, including the saponin-based Matrix-M adjuvant, which likely broadens epitope recognition and elicits a Th1-dominant immune response capable of enhancing humoral responses.
• Safety analyses indicated that these additional doses were well tolerated, with no new safety signals identified. 
• Overall, the findings support the use of booster doses to enhance and prolong immunity and suggest continued utility of this vaccine platform amid evolving virus variants in both adults and adolescents.

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