Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Philip J.M Brouwer,Julia M Giezen,Gius Kerster,Hannah L Turner,Karlijn Van Der Straten,Rashmi Ravichandran,Tom G Caniels,Virginie Chesnais,Cynthia A Van Der Linden,Marloes Grobben,Raphaël Ho Tsong Fang,Judith A Burger,Nidhal Kahlaoui,Kwinten Sliepen,Rogier W Sanders,Edith E Schermer,Andrew B Ward,Marlon De Gast,Julien Villaudy,Yoann Aldon,Sylvie Van Der Werf,Vanessa Contreras,Max Crispin,Joel D Allen,Yme U Van Der Velden,Meliawati Poniman,Mathieu Claireaux,Roger Le Grand,Godelieve J De Bree,Ségolène Diry,Nisreen M.A Okba,Eric Ginoux,Yasunori Watanabe,Julien Lemaître,Neil P King,Romain Marlin,Catherine Chapon,Pauline Maisonnasse,Thibaut Naninck,Jelle Van Schooten,Ilja Bontjer,Bart L Haagmans,Mitch Brinkkemper,Nathalie Dereuddre‐Bosquet ,Anna Z Mykytyn ,Mariëlle J Van Breemen

doi:10.1016/j.cell.2021.01.035

Abstract

SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe and infected more than 100 million individuals since late 2019
SARS-CoV-2 S proteins can be displayed on twocomponent I53-50 nanoparticles The computationally designed I53-50 nanoparticle (I53-50NP) constitutes 20 trimeric (I53-50A or variants thereof) and 12 pentameric (I53-50B.4PT1) subunits that self-assemble to form monodisperse icosahedral particles with a diameter of $30 nm (Bale et al, 2016)
The fusion protein was purified from transfected human embryonic kidney (HEK) 293F cell supernatant using nickel-nitrilotriacetic acid (Ni-NTA) purification followed by size exclusion chromatography (SEC)

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe and infected more than 100 million individuals since late 2019 (https://covid19.who.int/). SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), which manifests itself as a mild respiratory illness in most infected individuals but can lead to acute respiratory distress syndrome and death in a significant percentage of cases. Recent studies suggest that SARS-CoV-2-specific neutralizing antibody (NAb) titers are an important immune correlate of protection (Addetia et al, 2020; Yu et al, 2020). This is supported by several passive immunization studies showing that administration of potent neutralizing SARS-CoV-2-specific monoclonal antibodies (mAbs) can significantly reduce lung viral loads

Methods

Results

Discussion

Conclusion