Time-dependent enhancement of mRNA vaccines by 4-1BB costimulation
mRNA vaccines have demonstrated efficacy against COVID-19. However, concerns regarding waning immunity and breakthrough infections have motivated the development of next-generation vaccines with enhanced efficacy. In this study, we investigated the impact of 4-1BB costimulation on immune responses elicited by mRNA vaccines in mice. We first vaccinated mice with an mRNA vaccine encoding the SARS-CoV-2 spike antigen like the Moderna and Pfizer-BioNTech vaccines, followed by administration of 4-1BB costimulatory antibodies at various times post-vaccination. Administering 4-1BB costimulatory antibodies during the priming phase did not enhance immune responses. However, administering 4-1BB costimulatory antibodies after 96 hours elicited a significant improvement in CD8 T cell responses, leading to enhanced protection against breakthrough infections. A similar improvement in immune responses was observed with multiple mRNA vaccines, including vaccines against common cold coronavirus, human immunodeficiency virus (HIV), and arenavirus. These findings demonstrate a time-dependent effect by 4-1BB costimulation and provide insights for developing improved mRNA vaccines.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 04. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sanchez, Sarah [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 25.03.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2024.03.01.582992 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369861574 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369861574 | ||
| 003 | DE-627 | ||
| 005 | 20240325235248.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240318s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2024.03.01.582992 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1346.xml |
| 035 | |a (DE-627)NLM369861574 | ||
| 035 | |a (NLM)38496467 | ||
| 035 | |a (PII)2024.03.01.582992 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sanchez, Sarah |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Time-dependent enhancement of mRNA vaccines by 4-1BB costimulation |
| 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 25.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a mRNA vaccines have demonstrated efficacy against COVID-19. However, concerns regarding waning immunity and breakthrough infections have motivated the development of next-generation vaccines with enhanced efficacy. In this study, we investigated the impact of 4-1BB costimulation on immune responses elicited by mRNA vaccines in mice. We first vaccinated mice with an mRNA vaccine encoding the SARS-CoV-2 spike antigen like the Moderna and Pfizer-BioNTech vaccines, followed by administration of 4-1BB costimulatory antibodies at various times post-vaccination. Administering 4-1BB costimulatory antibodies during the priming phase did not enhance immune responses. However, administering 4-1BB costimulatory antibodies after 96 hours elicited a significant improvement in CD8 T cell responses, leading to enhanced protection against breakthrough infections. A similar improvement in immune responses was observed with multiple mRNA vaccines, including vaccines against common cold coronavirus, human immunodeficiency virus (HIV), and arenavirus. These findings demonstrate a time-dependent effect by 4-1BB costimulation and provide insights for developing improved mRNA vaccines | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Dangi, Tanushree |e verfasserin |4 aut | |
| 700 | 1 | |a Awakoaiye, Bakare |e verfasserin |4 aut | |
| 700 | 1 | |a Irani, Nahid |e verfasserin |4 aut | |
| 700 | 1 | |a Fourati, Slim |e verfasserin |4 aut | |
| 700 | 1 | |a Richner, Justin |e verfasserin |4 aut | |
| 700 | 1 | |a Penaloza-MacMaster, Pablo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv : the preprint server for biology |d 2020 |g (2024) vom: 04. März |w (DE-627)NLM31090014X |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:04 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2024.03.01.582992 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 04 |c 03 | ||