tetano
Editor, Senior Moderator
Cell Rep
. 2024 Aug 2;43(8):114567.
doi: 10.1016/j.celrep.2024.114567. Online ahead of print. Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1
Alexander Muik[SUP] 1 [/SUP], Jasmin Quandt[SUP] 1 [/SUP], Bonny Gaby Lui[SUP] 1 [/SUP], Maren Bacher[SUP] 1 [/SUP], Sebastian Lutz[SUP] 1 [/SUP], Maika Grünenthal[SUP] 1 [/SUP], Aras Toker[SUP] 1 [/SUP], Jessica Grosser[SUP] 1 [/SUP], Orkun Ozhelvaci[SUP] 1 [/SUP], Olga Blokhina[SUP] 1 [/SUP], Svetlana Shpyro[SUP] 1 [/SUP], Isabel Vogler[SUP] 1 [/SUP], Nadine Salisch[SUP] 1 [/SUP], Özlem Türeci[SUP] 2 [/SUP], Ugur Sahin[SUP] 3 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure histories become increasingly complex through original and variant-adapted vaccines and infections with viral variants. Upon exposure to the highly altered Omicron spike glycoprotein, pre-immunized individuals predominantly mount recall responses of Wuhan-Hu-1 (wild-type)-imprinted memory B (B[SUB]MEM[/SUB]) cells mostly targeting conserved non-neutralizing epitopes, leading to diminished Omicron neutralization. We investigated the impact of imprinting in individuals double/triple vaccinated with a wild-type-strain-based mRNA vaccine who, thereafter, had two consecutive exposures to Omicron BA.1 spike (breakthrough infection followed by BA.1-adapted vaccine). We found that depletion of conserved epitope-recognizing antibodies using a wild-type spike bait results in strongly diminished BA.1 neutralization. Furthermore, spike-specific B[SUB]MEM[/SUB] cells recognizing conserved epitopes are much more prevalent than BA.1-specific B[SUB]MEM[/SUB] cells. Our observations suggest that imprinted B[SUB]MEM[/SUB] cell recall responses limit the induction of strain-specific responses even after two consecutive BA.1 spike exposures. Vaccine adaptation strategies need to consider that prior SARS-CoV-2 infections and vaccinations may cause persistent immune imprinting.
Keywords: BNT162b2; CP: Immunology; Omicron; SARS-CoV-2; breakthrough infection; immune imprinting; memory B cells; neutralizing antibody; original antigenic sin.
. 2024 Aug 2;43(8):114567.
doi: 10.1016/j.celrep.2024.114567. Online ahead of print. Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1
Alexander Muik[SUP] 1 [/SUP], Jasmin Quandt[SUP] 1 [/SUP], Bonny Gaby Lui[SUP] 1 [/SUP], Maren Bacher[SUP] 1 [/SUP], Sebastian Lutz[SUP] 1 [/SUP], Maika Grünenthal[SUP] 1 [/SUP], Aras Toker[SUP] 1 [/SUP], Jessica Grosser[SUP] 1 [/SUP], Orkun Ozhelvaci[SUP] 1 [/SUP], Olga Blokhina[SUP] 1 [/SUP], Svetlana Shpyro[SUP] 1 [/SUP], Isabel Vogler[SUP] 1 [/SUP], Nadine Salisch[SUP] 1 [/SUP], Özlem Türeci[SUP] 2 [/SUP], Ugur Sahin[SUP] 3 [/SUP]
Affiliations
- PMID: 39097927
- DOI: 10.1016/j.celrep.2024.114567
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure histories become increasingly complex through original and variant-adapted vaccines and infections with viral variants. Upon exposure to the highly altered Omicron spike glycoprotein, pre-immunized individuals predominantly mount recall responses of Wuhan-Hu-1 (wild-type)-imprinted memory B (B[SUB]MEM[/SUB]) cells mostly targeting conserved non-neutralizing epitopes, leading to diminished Omicron neutralization. We investigated the impact of imprinting in individuals double/triple vaccinated with a wild-type-strain-based mRNA vaccine who, thereafter, had two consecutive exposures to Omicron BA.1 spike (breakthrough infection followed by BA.1-adapted vaccine). We found that depletion of conserved epitope-recognizing antibodies using a wild-type spike bait results in strongly diminished BA.1 neutralization. Furthermore, spike-specific B[SUB]MEM[/SUB] cells recognizing conserved epitopes are much more prevalent than BA.1-specific B[SUB]MEM[/SUB] cells. Our observations suggest that imprinted B[SUB]MEM[/SUB] cell recall responses limit the induction of strain-specific responses even after two consecutive BA.1 spike exposures. Vaccine adaptation strategies need to consider that prior SARS-CoV-2 infections and vaccinations may cause persistent immune imprinting.
Keywords: BNT162b2; CP: Immunology; Omicron; SARS-CoV-2; breakthrough infection; immune imprinting; memory B cells; neutralizing antibody; original antigenic sin.