Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals
Immunization with mosaic-8b [60-mer nanoparticles presenting 8 SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated effects of prior COVID-19 vaccinations in non-human primates and mice on sarbecovirus response breadths elicited by mosaic-8b, admix-8b (8 homotypics), and homotypic SARS-CoV-2, finding greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate-mapping in which antibodies derived from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced with mosaic-8b boosting, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19 vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 09. Feb. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cohen, Alexander A [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibody |
|---|
| Anmerkungen: |
Date Revised 26.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2024.02.08.576722 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368607569 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368607569 | ||
| 003 | DE-627 | ||
| 005 | 20240229155339.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240219s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2024.02.08.576722 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1306.xml |
| 035 | |a (DE-627)NLM368607569 | ||
| 035 | |a (NLM)38370696 | ||
| 035 | |a (PII)2024.02.08.576722 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cohen, Alexander A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Immunization with mosaic-8b [60-mer nanoparticles presenting 8 SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated effects of prior COVID-19 vaccinations in non-human primates and mice on sarbecovirus response breadths elicited by mosaic-8b, admix-8b (8 homotypics), and homotypic SARS-CoV-2, finding greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate-mapping in which antibodies derived from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced with mosaic-8b boosting, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19 vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential | ||
| 650 | 4 | |a Preprint | |
| 650 | 4 | |a Antibody | |
| 650 | 4 | |a Immune Imprinting | |
| 650 | 4 | |a Macaque and Mouse Models | |
| 650 | 4 | |a Mosaic-8b RBD-nanoparticle | |
| 650 | 4 | |a Original Antigenic Sin | |
| 650 | 4 | |a Primary Addiction | |
| 650 | 4 | |a RBD | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Sarbecovirus | |
| 650 | 4 | |a Vaccination | |
| 700 | 1 | |a Keeffe, Jennifer R |e verfasserin |4 aut | |
| 700 | 1 | |a Schiepers, Ariën |e verfasserin |4 aut | |
| 700 | 1 | |a Dross, Sandra E |e verfasserin |4 aut | |
| 700 | 1 | |a Greaney, Allison J |e verfasserin |4 aut | |
| 700 | 1 | |a Rorick, Annie V |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Gnanapragasam, Priyanthi N P |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Chengcheng |e verfasserin |4 aut | |
| 700 | 1 | |a West, Anthony P |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Ramsingh, Arlene I |e verfasserin |4 aut | |
| 700 | 1 | |a Erasmus, Jesse H |e verfasserin |4 aut | |
| 700 | 1 | |a Pata, Janice D |e verfasserin |4 aut | |
| 700 | 1 | |a Muramatsu, Hiromi |e verfasserin |4 aut | |
| 700 | 1 | |a Pardi, Norbert |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Paulo J C |e verfasserin |4 aut | |
| 700 | 1 | |a Baxter, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Cruz, Rita |e verfasserin |4 aut | |
| 700 | 1 | |a Quintanar-Audelo, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Robb, Ellis |e verfasserin |4 aut | |
| 700 | 1 | |a Serrano-Amatriain, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Magneschi, Leonardo |e verfasserin |4 aut | |
| 700 | 1 | |a Fotheringham, Ian G |e verfasserin |4 aut | |
| 700 | 1 | |a Fuller, Deborah H |e verfasserin |4 aut | |
| 700 | 1 | |a Victora, Gabriel D |e verfasserin |4 aut | |
| 700 | 1 | |a Bjorkman, Pamela J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv : the preprint server for biology |d 2020 |g (2024) vom: 09. Feb. |w (DE-627)NLM31090014X |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:09 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2024.02.08.576722 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 09 |c 02 | ||