tetano
Editor, Senior Moderator
ACS Infect Dis
. 2024 Jan 28.
doi: 10.1021/acsinfecdis.3c00483. Online ahead of print. Heterologous Sarbecovirus Receptor Binding Domains as Scaffolds for SARS-CoV-2 Receptor Binding Motif Presentation
Blake M Hauser[SUP] 1 [/SUP], Maya Sangesland[SUP] 1 [/SUP], Evan C Lam[SUP] 1 [/SUP], Kerri J St Denis[SUP] 1 [/SUP], Maegan L Sheehan[SUP] 1 [/SUP], Mya L Vu[SUP] 1 [/SUP], Agnes H Cheng[SUP] 1 [/SUP], Sophia Sordilla[SUP] 1 [/SUP], Dana Thornlow Lamson[SUP] 1 2 [/SUP], Ahmad W Almawi[SUP] 3 [/SUP], Alejandro B Balazs[SUP] 1 [/SUP], Daniel Lingwood[SUP] 1 [/SUP], Aaron G Schmidt[SUP] 1 2 [/SUP]
Affiliations
Structure-guided rational immunogen design can generate optimized immunogens that elicit a desired humoral response. Design strategies often center on targeting conserved sites on viral glycoproteins that will ultimately confer potent neutralization. For SARS-CoV-2 (SARS-2), the surface-exposed spike glycoprotein includes a broadly conserved portion, the receptor binding motif (RBM), that is required to engage the host cellular receptor, ACE2. Expanding humoral responses to this site may result in a more potent neutralizing antibody response against diverse sarbecoviruses. Here, we used a "resurfacing" approach and iterative design cycles to graft the SARS-2 RBM onto heterologous sarbecovirus scaffolds. The scaffolds were selected to vary the antigenic distance relative to SARS-2 to potentially focus responses to RBM. Multimerized versions of these immunogens elicited broad neutralization against sarbecoviruses in the context of preexisting SARS-2 immunity. These validated engineering approaches can help inform future immunogen design efforts for sarbecoviruses and are generally applicable to other viruses.
Keywords: SARS-CoV-2; coronavirus; immune imprinting.
. 2024 Jan 28.
doi: 10.1021/acsinfecdis.3c00483. Online ahead of print. Heterologous Sarbecovirus Receptor Binding Domains as Scaffolds for SARS-CoV-2 Receptor Binding Motif Presentation
Blake M Hauser[SUP] 1 [/SUP], Maya Sangesland[SUP] 1 [/SUP], Evan C Lam[SUP] 1 [/SUP], Kerri J St Denis[SUP] 1 [/SUP], Maegan L Sheehan[SUP] 1 [/SUP], Mya L Vu[SUP] 1 [/SUP], Agnes H Cheng[SUP] 1 [/SUP], Sophia Sordilla[SUP] 1 [/SUP], Dana Thornlow Lamson[SUP] 1 2 [/SUP], Ahmad W Almawi[SUP] 3 [/SUP], Alejandro B Balazs[SUP] 1 [/SUP], Daniel Lingwood[SUP] 1 [/SUP], Aaron G Schmidt[SUP] 1 2 [/SUP]
Affiliations
- PMID: 38281136
- DOI: 10.1021/acsinfecdis.3c00483
Structure-guided rational immunogen design can generate optimized immunogens that elicit a desired humoral response. Design strategies often center on targeting conserved sites on viral glycoproteins that will ultimately confer potent neutralization. For SARS-CoV-2 (SARS-2), the surface-exposed spike glycoprotein includes a broadly conserved portion, the receptor binding motif (RBM), that is required to engage the host cellular receptor, ACE2. Expanding humoral responses to this site may result in a more potent neutralizing antibody response against diverse sarbecoviruses. Here, we used a "resurfacing" approach and iterative design cycles to graft the SARS-2 RBM onto heterologous sarbecovirus scaffolds. The scaffolds were selected to vary the antigenic distance relative to SARS-2 to potentially focus responses to RBM. Multimerized versions of these immunogens elicited broad neutralization against sarbecoviruses in the context of preexisting SARS-2 immunity. These validated engineering approaches can help inform future immunogen design efforts for sarbecoviruses and are generally applicable to other viruses.
Keywords: SARS-CoV-2; coronavirus; immune imprinting.