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Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery.

Cuiping LiuLingshu WangJonah S MerriamWei ShiEun Sung YangYi ZhangMan ChenWing-Pui KongCheng ChengYaroslav TsybovskyTyler StephensRaffaello VerardiKwanyee LeungCody SteinAdam S OliaDarcy R HarrisMisook ChoeBaoshan ZhangBarney S GrahamPeter D KwongRichard A KoupAmarendra PeguJohn R Mascola
Published in: NPJ vaccines (2023)
While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P on a HBsAg core. These S6P-HBsAgs bound diverse domain-specific SARS-CoV-2 monoclonal antibodies. In mice with and without a HBV pre-vaccination, DNA immunization with S6P-HBsAgs elicited significantly more potent and durable neutralizing antibody (nAb) responses against diverse SARS-CoV-2 strains than that of soluble S2P or S6P, or full-length S2P with its coding sequence matching mRNA-1273. The nAb responses elicited by S6P-HBsAgs persisted substantially longer than by soluble S2P or S6P and appeared to be enhanced by HBsAg pre-exposure. These data show that genetic delivery of SARS-CoV-2 S6P-HBsAg nanoparticles can elicit greater and more durable nAb responses than non-nanoparticle forms of stabilized spike. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2.
Keyphrases
  • sars cov
  • hepatitis b virus
  • respiratory syndrome coronavirus
  • wild type
  • advanced non small cell lung cancer
  • escherichia coli
  • liver failure
  • single molecule
  • tyrosine kinase
  • anti inflammatory
  • artificial intelligence