Academic Journal
Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
| العنوان: | Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine |
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| المؤلفون: | Eugenia Z. Ong, Jia Xin Yee, Justin S. G. Ooi, Ayesa Syenina, Ruklanthi de Alwis, Shiwei Chen, Jean X. Y. Sim, Shirin Kalimuddin, Yan Shan Leong, Yvonne F. Z. Chan, Rose Sekulovich, Brian M. Sullivan, Kelly Lindert, Sean B. Sullivan, Pad Chivukula, Steven G. Hughes, Jenny G. Low, Eng Eong Ooi, Kuan Rong Chan |
| المصدر: | npj Vaccines, Vol 7, Iss 1, Pp 1-9 (2022) |
| بيانات النشر: | Nature Portfolio, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Abstract Remarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. An alternative form of the mRNA vaccine is the self-amplifying mRNA (sa-mRNA) vaccine, which encodes an alphavirus replicase that self-amplifies the full-length mRNA and SARS-CoV-2 spike (S) transgene. However, early-phase clinical trials of sa-mRNA COVID-19 vaccine candidates have questioned the potential of this platform to develop potent vaccines. We examined the immune gene response to a candidate sa-mRNA vaccine against COVID-19, ARCT-021, and compared our findings to the host response to other forms of vaccines. In blood samples from healthy volunteers that participated in a phase I/II clinical trial, greater induction of transcripts involved in Toll-like receptor (TLR) signalling, antigen presentation and complement activation at 1 day post-vaccination was associated with higher anti-S antibody titers. Conversely, transcripts involved in T-cell maturation at day 7 post-vaccination informed the magnitude of eventual S-specific T-cell responses. The transcriptomic signature for ARCT-021 vaccination strongly correlated with live viral vector vaccines, adjuvanted vaccines and BNT162b2 1 day post-vaccination. Moreover, the ARCT-021 signature correlated with day 7 YF17D live-attenuated vaccine transcriptomic responses. Altogether, our findings show that sa-mRNA vaccination induces innate immune responses that are associated with the development of adaptive immunity from other forms of vaccines, supporting further development of this vaccine platform for clinical application. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2059-0105 |
| Relation: | https://doaj.org/toc/2059-0105 |
| DOI: | 10.1038/s41541-022-00573-y |
| URL الوصول: | https://doaj.org/article/f164a1f335254aad9b2305f3200a7da5 |
| رقم الانضمام: | edsdoj.f164a1f335254aad9b2305f3200a7da5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20590105 |
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| DOI: | 10.1038/s41541-022-00573-y |