TY - JOUR
T1 - Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice
AU - Mabrouk, Moustafa T.
AU - Chiem, Kevin
AU - Rujas, Edurne
AU - Huang, Wei Chiao
AU - Jahagirdar, Dushyant
AU - Quinn, Breandan
AU - Nair, Meera Surendran
AU - Nissly, Ruth H.
AU - Cavener, Victoria S.
AU - Boyle, Nina R.
AU - Sornberger, Ty A.
AU - Kuchipudi, Suresh V.
AU - Ortega, Joaquin
AU - Julien, Jean Philippe
AU - Martinez-Sobrido, Luis
AU - Lovell, Jonathan
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved;
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1126/sciadv.abj1476
DO - 10.1126/sciadv.abj1476
M3 - Article
C2 - 34851667
AN - SCOPUS:85120696360
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 49
M1 - eabj1476
ER -