SARS-CoV-2 mRNA vaccine requires signal peptide to induce antibody responses

Mo, Chuncong; Li, Xiao; Wu, Qianying; Fan, Ye; Liu, Donglan; Zhu, Yuhui; Yang, Yujie; Liao, Xiaohong; Zhou, Zhichao; Zhou, Liling; Li, Qiuru; Zhang, Qiong; Liu, Wenkuan; Zhou, Rong; Tian, Xingui

doi:10.1016/j.vaccine.2023.09.059

Cited by 3 publications

(1 citation statement)

References 40 publications

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“…These strategies primarily involved designing new lipid carrier materials to enhance protein expression [ 15 ], introducing sequences to make the translated proteins form polymers to increase immunogenicity [ 16 , 17 ], optimizing new 5’ and 3’ UTR sequences to regulate translation [ 18 ], utilizing circular RNA to avoid degradation [ 13 ], and applying self-amplifying RNA to augment quantity [ 19 , 20 ]. Effective mRNA vaccine design against viruses requires specific signal sequences, without which there is no immune protective effect [ 21 ]. A previous study reported that designing a human kappa immunoglobulin signal sequence in an mRNA vaccine elicited a stronger immune response against the Ebola virus than the WT signal sequence [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection

Zhang,

Zhai,

Huang

et al. 2024

J Nanobiotechnol

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The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.

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Section: Introductionmentioning

confidence: 99%

Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection

Zhang,

Zhai,

Huang

et al. 2024

J Nanobiotechnol

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In Silico Design of a Trans‐Amplifying RNA‐Based Vaccine against SARS‐CoV‐2 Structural Proteins

Nafian,

Soleymani,

Pourmanouchehri

et al. 2024

Advances in Virology

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Nucleic acid‐based vaccines allow scalable, rapid, and cell‐free vaccine production in response to an emerging disease such as the current COVID‐19 pandemic. Here, we objected to the design of a multiepitope mRNA vaccine against the structural proteins of SARS‐CoV‐2. Through an immunoinformatic approach, promising epitopes were predicted for the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Fragments rich in overlapping epitopes were selected based on binding affinities with HLA classes I and II for the specific presentation to B and T lymphocytes. Two constructs were designed by fusing the fragments in different arrangements via GG linkers. Construct 1 showed better structural properties and interactions with toll‐like receptor 2 (TLR‐2), TLR‐3, and TLR‐4 during molecular docking and dynamic simulation. A 50S ribosomal L7/L12 adjuvant was added to its N‐terminus to improve stability and immunogenicity. The final RNA sequence was used to design a trans‐amplifying RNA (taRNA) vaccine in a split‐vector system. It consists of two molecules: a nonreplicating RNA encoding a trans‐acting replicase to amplify the second one, a trans‐replicon (TR) RNA encoding the vaccine protein. Overall, the immune response simulation detected that activated B and T lymphocytes and increased memory cell formation. Macrophages and dendritic cells proliferated continuously, and IFN‐γ and cytokines like IL‐2 were released highly.

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The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems

Parvin,

Mandal,

Joo

2024

Pharmaceutics

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The COVID-19 pandemic has significantly accelerated progress in RNA-based therapeutics, particularly through the successful development and global rollout of mRNA vaccines. This review delves into the transformative impact of the pandemic on RNA therapeutics, with a strong focus on lipid nanoparticles (LNPs) as a pivotal delivery platform. LNPs have proven to be critical in enhancing the stability, bioavailability, and targeted delivery of mRNA, facilitating the unprecedented success of vaccines like those developed by Pfizer-BioNTech and Moderna. Beyond vaccines, LNP technology is being explored for broader therapeutic applications, including treatments for cancer, rare genetic disorders, and infectious diseases. This review also discusses emerging RNA delivery systems, such as polymeric nanoparticles and viral vectors, which offer alternative strategies to overcome existing challenges related to stability, immune responses, and tissue-specific targeting. Additionally, we examine the pandemic’s influence on regulatory processes, including the fast-tracked approvals for RNA therapies, and the surge in research funding that has spurred further innovation in the field. Public acceptance of RNA-based treatments has also grown, laying the groundwork for future developments in personalized medicine. By providing an in-depth analysis of these advancements, this review highlights the long-term impact of COVID-19 on the evolution of RNA therapeutics and the future of precision drug delivery technologies.

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SARS-CoV-2 mRNA vaccine requires signal peptide to induce antibody responses

Cited by 3 publications

References 40 publications

Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection

Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection

In Silico Design of a Trans‐Amplifying RNA‐Based Vaccine against SARS‐CoV‐2 Structural Proteins

The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems

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