학술논문
Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery
Document Type
article
Author
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
Source
npj Vaccines, Vol 8, Iss 1, Pp 1-10 (2023)
Subject
Language
English
ISSN
2059-0105
Abstract
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.