In Proceedings of the National Academy of Sciences of the United States of America
Recurrent spillovers of α- and β-coronaviruses (CoV) such as severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome-CoV, SARS-CoV-2, and possibly human CoV have caused serious morbidity and mortality worldwide. In this study, six receptor-binding domains (RBDs) derived from α- and β-CoV that are considered to have originated from animals and cross-infected humans were linked to a heterotrimeric scaffold, proliferating cell nuclear antigen (PCNA) subunits, PCNA1, PCNA2, and PCNA3. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens, like jewels in a crown. Prime-boost immunizations with 6RBD-np in mice induced significantly high Ab titers against RBD antigens derived from α- and β-CoV and increased interferon (IFN-γ) production, with full protection against the SARS-CoV-2 wild type and Delta challenges. The mosaic 6RBD-np has the potential to induce intergenus cross-reactivity and to be developed as a pan-CoV vaccine against future CoV spillovers.
Lee Dan Bi, Kim Hyojin, Jeong Ju Hwan, Jang Ui Soon, Jang Yuyeon, Roh Seokbeom, Jeon Hyunbum, Kim Eun Jeong, Han Su Yeon, Maeng Jin Young, Magez Stefan, Radwanska Magdalena, Mun Ji Young, Jun Hyun Sik, Lee Gyudo, Song Min-Suk, Lee Hye-Ra, Chung Mi Sook, Baek Yun Hee, Kim Kyung Hyun
2023-Jan-24
SARS-CoV-2, immune response, mosaic multivalent antigens, receptor-binding domain, spike
