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| Home > Publications database > AS04 drives superior cross-protective antibody response by increased NOTCH signaling of dendritic cells and proliferation of memory B cells. > print |
| Home > Publications database > AS04 drives superior cross-protective antibody response by increased NOTCH signaling of dendritic cells and proliferation of memory B cells. > print |
| 001 | 303489 | ||
| 005 | 20250815114532.0 | ||
| 024 | 7 | _ | |a 10.3389/fimmu.2025.1623405 |2 doi |
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| 100 | 1 | _ | |a D'Onofrio, Valentino |b 0 |
| 245 | _ | _ | |a AS04 drives superior cross-protective antibody response by increased NOTCH signaling of dendritic cells and proliferation of memory B cells. |
| 260 | _ | _ | |a Lausanne |c 2025 |b Frontiers Media |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The Gardasil-4® vaccine targets HPV types 6, 11, 16 and 18 and is formulated with amorphous alum. Cervarix® targets HPV types 16 and 18 using AS04 (Al(OH)3 + TLR4 agonist MPL) to enhance immune response. Cervarix elicits higher cross-protection against other high-risk HPV types, likely mediated by AS04.To investigate mechanisms of cross-neutralizing potential, six monozygotic twins (12 females aged 9-13 years) were vaccinated with either Cervarix or Gardasil-4 (2 doses, 6 months apart). Serum neutralizing antibody titers against HPV 6,16,18,31,33,45,52, and 58 were assessed pre-vaccination and 7 days post-second dose. Multi-omic single cell RNA and ATAC sequencing of PBMCs was performed at the latter timepoint.Cervarix generated higher cross-neutralizing antibody titers than Gardasil-4. Higher frequencies of dendritic cells and memory B cells were observed. Gene Set Enrichment Analysis (GSEA) indicated enhanced pathways related to NOTCH2 signaling in DCs and cell cycling/RNA translation in B cells, correlating positively with cross-neutralizing antibody titers. Increased chromatin accessability in genes related to NOTCH signaling in cDC1 was also observed. Cervarix-vaccinated subjects showed increased DC-to-memory B signaling, through upregulation of NOTCH ligands. Engagement of NOTCH was associated to BCL2 expression in memory B cells, supporting an anti-apoptotic state.Increased DC signaling, including NOTCH, through AS04 in Cervarix supports cell survival and sustained RNA translation in memory B cells, 7 days post-vaccination. This may enhance adaptive immune cell maturation, providing a mechanism that can lead to improved cross-reactivity. |
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| 650 | _ | 7 | |a HPV vaccine |2 Other |
| 650 | _ | 7 | |a adjuvant |2 Other |
| 650 | _ | 7 | |a dendritic cells |2 Other |
| 650 | _ | 7 | |a immune response |2 Other |
| 650 | _ | 7 | |a memory B cell |2 Other |
| 700 | 1 | _ | |a Santana, Ana Carolina |b 1 |
| 700 | 1 | _ | |a Pauwels, Marthe |b 2 |
| 700 | 1 | _ | |a Waerlop, Gwenn |b 3 |
| 700 | 1 | _ | |a Willems, Anthony |b 4 |
| 700 | 1 | _ | |a De Boever, Fien |b 5 |
| 700 | 1 | _ | |a Müller, Martin |0 P:(DE-He78)47d2c5b8ee00ab8a0c16e14137427579 |b 6 |u dkfz |
| 700 | 1 | _ | |a Sehr, Peter |b 7 |
| 700 | 1 | _ | |a Waterboer, Tim |0 P:(DE-He78)6b4ebb9791b983b5620c0caaf3468e30 |b 8 |u dkfz |
| 700 | 1 | _ | |a Leroux-Roels, Isabel |b 9 |
| 700 | 1 | _ | |a Sharma, Ashish A |b 10 |
| 700 | 1 | _ | |a Sékaly, Rafick Pierre |b 11 |
| 700 | 1 | _ | |a Leroux-Roels, Geert |b 12 |
| 773 | _ | _ | |a 10.3389/fimmu.2025.1623405 |g Vol. 16, p. 1623405 |0 PERI:(DE-600)2606827-8 |p 1623405 |t Frontiers in immunology |v 16 |y 2025 |x 1664-3224 |
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