Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery
Cuiping Liu,
Lingshu Wang,
Jonah S. Merriam,
Wei Shi,
Eun Sung Yang,
Yi Zhang,
Man Chen,
Wing-Pui Kong,
Cheng Cheng,
Yaroslav Tsybovsky,
Tyler Stephens,
Raffaello Verardi,
Kwanyee Leung,
Cody Stein,
Adam S. Olia,
Darcy R. Harris,
Misook Choe,
Baoshan Zhang,
Barney S. Graham,
Peter D. Kwong,
Richard A. Koup,
Amarendra Pegu,
John R. Mascola
Affiliations
Cuiping Liu
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Lingshu Wang
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Jonah S. Merriam
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Wei Shi
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Eun Sung Yang
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Yi Zhang
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Man Chen
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Wing-Pui Kong
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Cheng Cheng
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Yaroslav Tsybovsky
Vaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Tyler Stephens
Vaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Raffaello Verardi
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Kwanyee Leung
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Cody Stein
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Adam S. Olia
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Darcy R. Harris
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Misook Choe
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Baoshan Zhang
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Barney S. Graham
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Peter D. Kwong
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Richard A. Koup
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Amarendra Pegu
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
John R. Mascola
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
Abstract 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.
