tetano
Editor, Senior Moderator
Nat Commun
. 2023 Oct 4;14(1):6195.
doi: 10.1038/s41467-023-41661-4. Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera
Geoffrey B Hutchinson[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Olubukola M Abiona[SUP] #[/SUP][SUP] 1 4 [/SUP], Cynthia T Ziwawo[SUP] 1 [/SUP], Anne P Werner[SUP] 1 5 [/SUP], Daniel Ellis[SUP] 2 6 [/SUP], Yaroslav Tsybovsky[SUP] 7 [/SUP], Sarah R Leist[SUP] 8 [/SUP], Charis Palandjian[SUP] 9 [/SUP], Ande West[SUP] 8 [/SUP], Ethan J Fritch[SUP] 10 [/SUP], Nianshuang Wang[SUP] 11 [/SUP], Daniel Wrapp[SUP] 11 [/SUP], Seyhan Boyoglu-Barnum[SUP] 1 [/SUP], George Ueda[SUP] 2 6 [/SUP], David Baker[SUP] 2 6 12 [/SUP], Masaru Kanekiyo[SUP] 1 [/SUP], Jason S McLellan[SUP] 11 [/SUP], Ralph S Baric[SUP] 8 10 [/SUP], Neil P King[SUP] 2 6 [/SUP], Barney S Graham[SUP] 13 [/SUP], Kizzmekia S Corbett-Helaire[SUP] 14 15 [/SUP]
Affiliations
Multivalent antigen display is a fast-growing area of interest toward broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains of notably mutable viruses. In coronaviruses, this work is predominantly aimed at targeting conserved epitopes of the receptor binding domain. However, targeting conserved non-RBD epitopes could limit the potential for antigenic escape. To explore new potential targets, we engineered protein nanoparticles displaying coronavirus prefusion-stabilized spike (CoV_S-2P) trimers derived from MERS-CoV, SARS-CoV-1, SARS-CoV-2, hCoV-HKU1, and hCoV-OC43 and assessed their immunogenicity in female mice. Monotypic SARS-1 nanoparticles elicit cross-neutralizing antibodies against MERS-CoV and protect against MERS-CoV challenge. MERS and SARS nanoparticles elicit S1-focused antibodies, revealing a conserved site on the S N-terminal domain. Moreover, mosaic nanoparticles co-displaying distinct CoV_S-2P trimers elicit antibody responses to distant cross-group antigens and protect male and female mice against MERS-CoV challenge. Our findings will inform further efforts toward the development of pan-coronavirus vaccines.
. 2023 Oct 4;14(1):6195.
doi: 10.1038/s41467-023-41661-4. Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera
Geoffrey B Hutchinson[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Olubukola M Abiona[SUP] #[/SUP][SUP] 1 4 [/SUP], Cynthia T Ziwawo[SUP] 1 [/SUP], Anne P Werner[SUP] 1 5 [/SUP], Daniel Ellis[SUP] 2 6 [/SUP], Yaroslav Tsybovsky[SUP] 7 [/SUP], Sarah R Leist[SUP] 8 [/SUP], Charis Palandjian[SUP] 9 [/SUP], Ande West[SUP] 8 [/SUP], Ethan J Fritch[SUP] 10 [/SUP], Nianshuang Wang[SUP] 11 [/SUP], Daniel Wrapp[SUP] 11 [/SUP], Seyhan Boyoglu-Barnum[SUP] 1 [/SUP], George Ueda[SUP] 2 6 [/SUP], David Baker[SUP] 2 6 12 [/SUP], Masaru Kanekiyo[SUP] 1 [/SUP], Jason S McLellan[SUP] 11 [/SUP], Ralph S Baric[SUP] 8 10 [/SUP], Neil P King[SUP] 2 6 [/SUP], Barney S Graham[SUP] 13 [/SUP], Kizzmekia S Corbett-Helaire[SUP] 14 15 [/SUP]
Affiliations
- PMID: 37794071
- DOI: 10.1038/s41467-023-41661-4
Multivalent antigen display is a fast-growing area of interest toward broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains of notably mutable viruses. In coronaviruses, this work is predominantly aimed at targeting conserved epitopes of the receptor binding domain. However, targeting conserved non-RBD epitopes could limit the potential for antigenic escape. To explore new potential targets, we engineered protein nanoparticles displaying coronavirus prefusion-stabilized spike (CoV_S-2P) trimers derived from MERS-CoV, SARS-CoV-1, SARS-CoV-2, hCoV-HKU1, and hCoV-OC43 and assessed their immunogenicity in female mice. Monotypic SARS-1 nanoparticles elicit cross-neutralizing antibodies against MERS-CoV and protect against MERS-CoV challenge. MERS and SARS nanoparticles elicit S1-focused antibodies, revealing a conserved site on the S N-terminal domain. Moreover, mosaic nanoparticles co-displaying distinct CoV_S-2P trimers elicit antibody responses to distant cross-group antigens and protect male and female mice against MERS-CoV challenge. Our findings will inform further efforts toward the development of pan-coronavirus vaccines.