Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice

Moustafa T. Mabrouk, Kevin Chiem, Edurne Rujas, Wei Chiao Huang, Dushyant Jahagirdar, Breandan Quinn, Meera Surendran Nair, Ruth H. Nissly, Victoria S. Cavener, Nina R. Boyle, Ty A. Sornberger, Suresh V. Kuchipudi, Joaquin Ortega, Jean Philippe Julien, Luis Martinez-Sobrido, Jonathan Lovell

Research output: Contribution to journalArticlepeer-review

Abstract

The COVID-19 pandemic has spurred interest in potent and thermostable SARS-CoV-2 vaccines. Here, we assess low-dose immunization with lyophilized nanoparticles decorated with recombinant SARS-CoV-2 antigens. The SARS-CoV-2 Spike glycoprotein or its receptor-binding domain (RBD; mouse vaccine dose, 0.1g) was displayed on liposomes incorporating a particle-inducing lipid, cobalt porphyrin-phospholipid (dose, 0.4 μg), along with monophosphoryl lipid A (dose, 0.16 μg) and QS-21 (dose, 0.16 μg). Following optimization of lyophilization conditions, Spike or RBD-decorated liposomes were effectively reconstituted and maintained conformational capacity for binding human angiotensin-converting enzyme 2 (hACE2) for at least a week when stored at 60°C in lyophilized but not liquid format. Prime-boost intramuscular vaccination of hACE2-transgenic mice with the reconstituted vaccine formulations induced effective antibody responses that inhibited RBD binding to hACE2 and neutralized pseudotyped and live SARS-CoV-2. Two days following viral challenge, immunized transgenic mice cleared the virus and were fully protected from lethal disease.

Original languageEnglish (US)
Article numbereabj1476
JournalScience Advances
Volume7
Issue number49
DOIs
StatePublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • General

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