AI Article Synopsis
- The study explores new mRNA vaccine strategies to enhance effectiveness against COVID-19, focusing on specific protein domains of the virus instead of the full-length spike protein.
- The candidate vaccine mRNA-1283, combining the N-terminal domain and receptor binding domain, shows better antigen expression, stronger antibody responses, and improved stability compared to existing vaccines.
- In animal tests, mRNA-1283 elicits equal or greater immune protection against various COVID-19 variants, supporting its advancement to clinical trials for further evaluation.
Article Abstract
With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD-linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273-immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/scitranslmed.adf4100 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clinical advances of mRNA vaccines for cancer immunotherapy.
Med
January 2025
Center for Nanomedicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
The development of mRNA vaccines represents a significant advancement in cancer treatment, with more than 120 clinical trials to date demonstrating their potential across various malignancies, including lung, breast, prostate, melanoma, and more challenging cancers such as pancreatic and brain tumors. These vaccines work by encoding tumor-specific antigens and immune-stimulating molecules, effectively activating the immune system to target and eliminate cancer cells. Despite these promising advancements, significant challenges remain, particularly in achieving efficient delivery and precise regulation of the immune response.
View Article and Find Full Text PDFVisualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates.
Mol Ther
January 2025
Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Department of Chemical Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA, 02139; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University; Cambridge, MA, USA, 02139; Howard Hughes Medical Institute; Chevy Chase, MD, USA, 20815; Department of Materials Science of Engineering; Massachusetts Institute of Technology; Cambridge, MA, USA, 02139. Electronic address:
mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following i.
View Article and Find Full Text PDFMechanism of THBS1 Regulation of MDCK Cell Proliferation and Apoptosis Through TGF-β/Smad Signalling.
Int J Mol Sci
January 2025
Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Lanzhou 730030, China.
Madin-Darby Canine Kidney (MDCK) cells are a key cell line for influenza vaccine production, due to their high viral yield and low mutation resistance. In our laboratory, we established a tertiary cell bank (called M60) using a standard MDCK cell line imported from American Type Culture Collection (ATCC) in the USA. Due to their controversial tumourigenicity, we domesticated non-tumourigenic MDCK cells (named CL23) for influenza vaccine production via monoclonal screening in the early stage of this study, and the screened CL23 cells were characterised based on their low proliferative capacity, which had certain limitations in terms of expanding their production during cell resuscitation.
View Article and Find Full Text PDFExpanding the Potential of Circular RNA (CircRNA) Vaccines: A Promising Therapeutic Approach.
Int J Mol Sci
January 2025
State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education Ministry, College of Life Sciences, Hunan Normal University, Changsha 410081, China.
In recent years, circular RNAs (circRNAs) have garnered significant attention due to their unique structure and function, positioning them as promising candidates for next-generation vaccines. The circRNA vaccine, as an RNA vaccine, offers significant advantages in preventing infectious diseases by serving as a vector for protein expression through non-canonical translation. Notably, circRNA vaccines have demonstrated enduring antigenic expression and generate a larger percentage of neutralizing antibodies compared to mRNA vaccines administered at the same dosage.
View Article and Find Full Text PDFRecommendation for the use of respiratory syncytial virus vaccines.
J Microbiol Immunol Infect
January 2025
Division of Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taiwan.
Respiratory syncytial virus (RSV) is the most common pathogen for young children hospitalized with bronchiolitis and pneumonia. Most infections occur below 1 year of age. RSV is also a significant viral pathogen for adults with respiratory tract infection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!