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

• Published in: Science advances 2021-12, Vol.7 (49), p.eabj1476-eabj1476
• Main Authors: Mabrouk, Moustafa T, Chiem, Kevin, Rujas, Edurne, Huang, Wei-Chiao, Jahagirdar, Dushyant, Quinn, Breandan, Surendran Nair, Meera, Nissly, Ruth H, Cavener, Victoria S, Boyle, Nina R, Sornberger, Ty A, Kuchipudi, Suresh V, Ortega, Joaquin, Julien, Jean-Philippe, Martinez-Sobrido, Luis, Lovell, Jonathan
• Format: Article
• Language: English
• Subjects: Biomedicine and Life Sciences; Coronavirus; Life Sciences; Materials Science; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abj1476

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, 0.1 μg) 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.