tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2023 Jan 24;120(4):e2208425120.
doi: 10.1073/pnas.2208425120. Epub 2023 Jan 20.
Mosaic RBD nanoparticles induce intergenus cross-reactive antibodies and protect against SARS-CoV-2 challenge
Dan Bi Lee[SUP] 1 [/SUP], Hyojin Kim[SUP] 2 [/SUP], Ju Hwan Jeong[SUP] 3 [/SUP], Ui Soon Jang[SUP] 1 4 [/SUP], Yuyeon Jang[SUP] 1 4 [/SUP], Seokbeom Roh[SUP] 1 4 [/SUP], Hyunbum Jeon[SUP] 5 [/SUP], Eun Jeong Kim[SUP] 1 [/SUP], Su Yeon Han[SUP] 1 [/SUP], Jin Young Maeng[SUP] 2 [/SUP], Stefan Magez[SUP] 6 7 8 [/SUP], Magdalena Radwanska[SUP] 6 9 [/SUP], Ji Young Mun[SUP] 10 [/SUP], Hyun Sik Jun[SUP] 1 4 [/SUP], Gyudo Lee[SUP] 1 4 [/SUP], Min-Suk Song[SUP] 3 [/SUP], Hye-Ra Lee[SUP] 1 4 [/SUP], Mi Sook Chung[SUP] 2 [/SUP], Yun Hee Baek[SUP] 3 [/SUP], Kyung Hyun Kim[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: SARS-CoV-2; immune response; mosaic multivalent antigens; receptor-binding domain; spike.
. 2023 Jan 24;120(4):e2208425120.
doi: 10.1073/pnas.2208425120. Epub 2023 Jan 20.
Mosaic RBD nanoparticles induce intergenus cross-reactive antibodies and protect against SARS-CoV-2 challenge
Dan Bi Lee[SUP] 1 [/SUP], Hyojin Kim[SUP] 2 [/SUP], Ju Hwan Jeong[SUP] 3 [/SUP], Ui Soon Jang[SUP] 1 4 [/SUP], Yuyeon Jang[SUP] 1 4 [/SUP], Seokbeom Roh[SUP] 1 4 [/SUP], Hyunbum Jeon[SUP] 5 [/SUP], Eun Jeong Kim[SUP] 1 [/SUP], Su Yeon Han[SUP] 1 [/SUP], Jin Young Maeng[SUP] 2 [/SUP], Stefan Magez[SUP] 6 7 8 [/SUP], Magdalena Radwanska[SUP] 6 9 [/SUP], Ji Young Mun[SUP] 10 [/SUP], Hyun Sik Jun[SUP] 1 4 [/SUP], Gyudo Lee[SUP] 1 4 [/SUP], Min-Suk Song[SUP] 3 [/SUP], Hye-Ra Lee[SUP] 1 4 [/SUP], Mi Sook Chung[SUP] 2 [/SUP], Yun Hee Baek[SUP] 3 [/SUP], Kyung Hyun Kim[SUP] 1 [/SUP]
Affiliations
- PMID: 36669119
- DOI: 10.1073/pnas.2208425120
Abstract
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.
Keywords: SARS-CoV-2; immune response; mosaic multivalent antigens; receptor-binding domain; spike.