XBB.1.5 Spike Protein COVID-19 Vaccine Induces Broadly Neutralizing and Cellular Immune Responses Against EG.5.1 and Emerging XBB Variants

Patel, N.; Trost, J. F.; Guebre-Xabier, M.; Zhou, H.; Norton, J.; Jiang, D.; Cai, Z.; Zhu, M.; Marchese, A. M.; Greene, A. M.; Mallory, R. M.; Kalkeri, R.; Dubovsky, F.; Smith, G.

doi:10.1101/2023.08.30.554497

bioRxiv · 10.1101/2023.08.30.554497

XBB.1.5 Spike Protein COVID-19 Vaccine Induces Broadly Neutralizing and Cellular Immune Responses Against EG.5.1 and Emerging XBB Variants

Patel, N.·Trost, J. F.·Guebre-Xabier, M.·Zhou, H.·Norton, J.·Jiang, D.·Cai, Z.·Zhu, M.·Marchese, A. M.·Greene, A. M.·Mallory, R. M.·Kalkeri, R.·Dubovsky, F.·Smith, G.

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Abstract

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. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. 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. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces cross-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. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023-2024 COVID-19 vaccination campaign.

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Patel, N., Trost, J. F., Guebre-Xabier, M., Zhou, H., Norton, J., Jiang, D., Cai, Z., Zhu, M., Marchese, A. M., Greene, A. M., Mallory, R. M., Kalkeri, R., Dubovsky, F., Smith, G.. 2023-08-31. XBB.1.5 Spike Protein COVID-19 Vaccine Induces Broadly Neutralizing and Cellular Immune Responses Against EG.5.1 and Emerging XBB Variants. https://doi.org/10.1101/2023.08.30.554497

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