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NVX-CoV2373 has been authorized for primary series use and as a homologous or heterologous booster in many countries globally.

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NVX-CoV2373, based on the Prototype (Wuhan-Hu-1) rS, was demonstrated to be well tolerated and immunogenic in humans 12, 13, with a vaccine efficacy of 90.4% (95% CI 82.9 to 94.6) against mild-to-severe disease in a Phase 3 clinical trial 14. Antigen particles are formulated with a saponin-based Matrix-M™ adjuvant 8, which has been shown to induce robust antibody responses that protect upper and lower airways in nonhuman primates 9 and polyfunctional Th1-biased CD4 + T cell responses 10, 11, 12. Proteins expressed in Sf9 insect cells are post-translationally modified with smaller and less processed N-linked glycans, helping critical epitopes for antibody binding remain exposed compared to proteins produced in mammalian cells 7. Protein antigens are manufactured in a baculovirus expression system using Spodoptera frugiperda moth cells (Sf9) that express glycoproteins with truncated N-linked glycans with a potential for enhanced epitope exposure. Spike protein trimers form particles surrounding a polysorbate-80 core, which may improve antigen uptake and processing. The Novavax COVID vaccine platform contains the full-length recombinant spike (rS) protein presented in its native trimeric and prefusion conformation 5, 6.

This change in vaccine composition highlights the need for robust immunologic evaluation of emerging Omicron XBB sub-variants. A vaccine strain and composition change to monovalent XBB.1.5-based vaccines have been supported by the World Health Organization (WHO), the European Medicines Agency (EMA), and the United States Food and Drug Administration (FDA) in anticipation of the Fall 2023–2024 booster campaigns 2, 3, 4.

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The need to update the vaccine strain has been signaled by a reduction of antibody-mediated immunity against Omicron XBB subvariants 1. Prior to recommendations for COVID-19 vaccine strain change and composition harmonization, COVID-19 vaccine options included monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + Omicron BA.4/5). Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023–2024 COVID-19 vaccination campaign. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4 + T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against SARS-CoV-2 Omicron XBB sub-variants.

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