mRNA Vaccines: Pioneering the Future of Vaccination

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "DNA and mRNA Vaccines".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 9691

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Guest Editor
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
Interests: covid; vaccine
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
Interests: biomimetic materials; nanomedicine against cancers; neurological disorders

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Guest Editor
Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Interests: PET/CT; COVID-19; Vaccine; Vaccination
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Special Issue Information

Dear Colleagues,

Amid the devastation of the COVID-19 pandemic, mRNA vaccines have risen to the occasion. While early IVT-mRNA was limited by instability, high immunogenicity, and poor translatability, current advances in mRNA synthesis have significantly enhanced antigen expression and protective immunity. Novel delivery vehicles such as lipid nanoparticles (LNPs) have extended the intracellular lifetime of mRNA vaccines from minutes to weeks and are capable of targeted delivery to specific cell types, such as lymphocytes. The current mRNA-LNP platform will not only be useful to demonstrate the use of mRNA vaccines for combatting COVID-19, but also to establish the LNP-mRNA platform as robust and generalizable to early incurable infectious diseases, such as Ebola, polio, lupus, aids, Zika, etc.

The impact of mRNA vaccines on cancer and infectious disease remains in its preliminary stages. Trials in animal-based models and human individuals exhibit substantial differences in expression and immune response. The mechanisms of these vaccines in animal models and humans also require further investigation.

To achieve a more extensive understanding of the recent scientific knowledge and current trends in mRNA vaccine development, this Special issue is focused on the recent scientific and technical advances including, but not limited to, mRNA vaccines. Based on your extensive knowledge and experience, we invite you to contribute an original report, original observation or review.

Dr. Zhongfeng Ye
Dr. Yu Zhao
Dr. Minghui Yang
Guest Editors

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Keywords

  • mRNA vaccine
  • lipid nanoparticles (LNPs)
  • mRNA-LNP platform
  • infectious diseases
  • cancer
  • immune response

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Published Papers (5 papers)

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Research

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16 pages, 5188 KiB  
Article
Immunogenicity and Efficacy of Combined mRNA Vaccine Against Influenza and SARS-CoV-2 in Mice Animal Models
by Elena P. Mazunina, Vladimir A. Gushchin, Evgeniia N. Bykonia, Denis A. Kleymenov, Andrei E. Siniavin, Sofia R. Kozlova, Evgenya A. Mukasheva, Elena V. Shidlovskaya, Nadezhda A. Kuznetsova, Evgeny V. Usachev, Vladimir I. Zlobin, Elena I. Burtseva, Roman A. Ivanov, Denis Y. Logunov and Alexander L. Gintsburg
Vaccines 2024, 12(11), 1206; https://doi.org/10.3390/vaccines12111206 - 24 Oct 2024
Cited by 1 | Viewed by 1532
Abstract
Background. The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and [...] Read more.
Background. The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines. There are currently no mRNA-based combined vaccines approved for use in humans. Some studies have shown that different mRNA components in a vaccine can interact to increase or decrease the immunogenicity and efficacy of the combined vaccine. Objectives. In the present study, we investigated the possibility of combining the mRNA vaccines, encoding seasonal influenza and SARS-CoV-2 antigens. In our previous works, both vaccine candidates have shown excellent immunogenicity and efficacy profiles in mice. Methods. The mRNA-LNPs were prepared by microfluidic mixing, immunogenicity in mice was assessed by hemagglutination inhibition assay, enzyme-linked immunoassay and virus neutralization assay. Immunological efficacy was assessed in a mouse viral challenge model. Results. In this work, we demonstrated that the individual mRNA components of the combined vaccine did not affect the immunogenicity level of each other. The combined vaccine demonstrated excellent protective efficacy, providing a 100% survival rate when mice were infected with the H1N1 influenza virus and reducing the viral load in the lungs. Four days after the challenge with SARS-CoV-2 EG.5.1.1., no viable virus and low levels of detectable viral RNA were observed in the lungs of vaccinated mice. Conclusions. The combination does not lead to mutual interference between the individual vaccines. We believe that such a combined mRNA-based vaccine could be a good alternative to separated human vaccinations for the prevention of COVID-19 and influenza. Full article
(This article belongs to the Special Issue mRNA Vaccines: Pioneering the Future of Vaccination)
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13 pages, 1786 KiB  
Article
Immunogenic Comparison of Nucleic Acid-Based Vaccines Administered by Pyro-Drive Jet Injector
by Jiayu A. Tai, Tomoyuki Nishikawa, Hiroki Hayashi, Yu-Diao Kuan, Kunihiko Yamashita and Hironori Nakagami
Vaccines 2024, 12(7), 757; https://doi.org/10.3390/vaccines12070757 - 9 Jul 2024
Viewed by 1330
Abstract
mRNA vaccines were successfully developed and approved for emergency use to fight coronavirus disease 2019. However, the effect of DNA vaccines against SARS-CoV-2 is considerably lower than that of mRNA vaccines. A pyro-drive jet injector (PJI) efficiently delivers plasmid DNA intradermally into animal [...] Read more.
mRNA vaccines were successfully developed and approved for emergency use to fight coronavirus disease 2019. However, the effect of DNA vaccines against SARS-CoV-2 is considerably lower than that of mRNA vaccines. A pyro-drive jet injector (PJI) efficiently delivers plasmid DNA intradermally into animal models. Here, we compared the immunogenic potential of DNA and mRNA vaccines in mice using the same platform. PJI was used to deliver naked mRNA and pDNA and their efficacy in inducing antigen expression and immune responses was assessed. Our results showed that PJI efficiently delivered mRNA into the skin, and a smaller effective dose than that of pDNA injection was required to achieve similar levels of antigen expression. The PJI-delivered CpG-free pDNA vaccine efficiently induced antigen-specific antibody production and a cell-mediated IFN-γ response compared to the mRNA vaccine, as well as the upregulation of inflammatory cytokines (IL-6, IFN-γ, and IL-1β) in the skin and lymph nodes. However, the intradermal mRNA vaccine was significantly less immunogenic than the standard intramuscular mRNA-lipid nanoparticle vaccine, despite equivalent mRNA dosages. Improvements in lipid nanoparticle and mRNA technology have revolutionized mRNA vaccines, and DNA vaccines can be similarly modified for higher clinical efficacy. Full article
(This article belongs to the Special Issue mRNA Vaccines: Pioneering the Future of Vaccination)
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16 pages, 2724 KiB  
Article
Assessment of Human SARS CoV-2-Specific T-Cell Responses Elicited In Vitro by New Computationally Designed mRNA Immunogens (COVARNA)
by Ignasi Esteban, Carmen Pastor-Quiñones, Lorena Usero, Elena Aurrecoechea, Lorenzo Franceschini, Arthur Esprit, Josep Lluís Gelpí, Francisco Martínez-Jiménez, Núria López-Bigas, Karine Breckpot, Kris Thielemans, Lorna Leal, Carmen Elena Gómez, Marta Sisteré-Oró, Andreas Meyerhans, Mariano Esteban, María José Alonso, Felipe García and Montserrat Plana
Vaccines 2024, 12(1), 15; https://doi.org/10.3390/vaccines12010015 - 22 Dec 2023
Viewed by 1814
Abstract
The COVID-19 pandemic has brought significant changes and advances in the field of vaccination, including the implementation and widespread use of encapsidated mRNA vaccines in general healthcare practice. Here, we present two new mRNAs expressing antigenic parts of the SARS-CoV-2 spike protein and [...] Read more.
The COVID-19 pandemic has brought significant changes and advances in the field of vaccination, including the implementation and widespread use of encapsidated mRNA vaccines in general healthcare practice. Here, we present two new mRNAs expressing antigenic parts of the SARS-CoV-2 spike protein and provide data supporting their functionality. The first mRNA, called RBD-mRNA, encodes a trimeric form of the virus spike protein receptor binding domain (RBD). The other mRNA, termed T-mRNA, codes for the relevant HLA I and II spike epitopes. The two mRNAs (COVARNA mRNAs) were designed to be used for delivery to cells in combination, with the RBD-mRNA being the primary source of antigen and the T-mRNA working as an enhancer of immunogenicity by supporting CD4 and CD8 T-cell activation. This innovative approach substantially differs from other available mRNA vaccines, which are largely directed to antibody production by the entire spike protein. In this study, we first show that both mRNAs are functionally transfected into human antigen-presenting cells (APCs). We obtained peripheral blood mononuclear cell (PBMC) samples from three groups of voluntary donors differing in their immunity against SARS-CoV-2: non-infected (naïve), infected-recovered (convalescent), and vaccinated. Using an established method of co-culturing autologous human dendritic cells (hDCs) with T-cells, we detected proliferation and cytokine secretion, thus demonstrating the ability of the COVARNA mRNAs to activate T-cells in an antigen-specific way. Interestingly, important differences in the intensity of the response between the infected-recovered (convalescent) and vaccinated donors were observed, with the levels of T-cell proliferation and cytokine secretion (IFNγ, IL-2R, and IL-13) being higher in the vaccinated group. In summary, our data support the further study of these mRNAs as a combined approach for future use as a vaccine. Full article
(This article belongs to the Special Issue mRNA Vaccines: Pioneering the Future of Vaccination)
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Review

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13 pages, 4324 KiB  
Review
The Recent Research Progress of the Tumor mRNA Vaccine
by Hao Zhao, Miying Li, Jiaren Zhou, Lidan Hu, Shaohong Lu and Pan Li
Vaccines 2024, 12(10), 1167; https://doi.org/10.3390/vaccines12101167 - 12 Oct 2024
Viewed by 2318
Abstract
Tumors have long posed a significant threat to human life and health, and the messenger ribonucleic acid (mRNA) vaccine is seen as an attractive approach for cancer immunotherapy due to its developmental simplicity, rapid manufacture, and increased immune safety and efficiency. In this [...] Read more.
Tumors have long posed a significant threat to human life and health, and the messenger ribonucleic acid (mRNA) vaccine is seen as an attractive approach for cancer immunotherapy due to its developmental simplicity, rapid manufacture, and increased immune safety and efficiency. In this review, we have summarized details of the developmental history of mRNA vaccines, discussed the basic molecular structure and the effect on the stable and translation level of mRNA, analyzed the underlying immune efficiency and mechanisms on tumors, and assessed the current status of clinical research. We explored the treatment and application prospects of mRNA vaccines, aiming to provide perspectives on the future of mRNA tumor vaccines for ongoing clinical research. Full article
(This article belongs to the Special Issue mRNA Vaccines: Pioneering the Future of Vaccination)
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22 pages, 10745 KiB  
Review
Rational Design of Lipid-Based Vectors for Advanced Therapeutic Vaccines
by Yufei Ma, Yiang Chen, Zilu Li and Yu Zhao
Vaccines 2024, 12(6), 603; https://doi.org/10.3390/vaccines12060603 - 31 May 2024
Viewed by 1696
Abstract
Recent advancements in vaccine delivery systems have seen the utilization of various materials, including lipids, polymers, peptides, metals, and inorganic substances, for constructing non-viral vectors. Among these, lipid-based nanoparticles, composed of natural, synthetic, or physiological lipid/phospholipid materials, offer significant advantages such as biocompatibility, [...] Read more.
Recent advancements in vaccine delivery systems have seen the utilization of various materials, including lipids, polymers, peptides, metals, and inorganic substances, for constructing non-viral vectors. Among these, lipid-based nanoparticles, composed of natural, synthetic, or physiological lipid/phospholipid materials, offer significant advantages such as biocompatibility, biodegradability, and safety, making them ideal for vaccine delivery. These lipid-based vectors can protect encapsulated antigens and/or mRNA from degradation, precisely tune chemical and physical properties to mimic viruses, facilitate targeted delivery to specific immune cells, and enable efficient endosomal escape for robust immune activation. Notably, lipid-based vaccines, exemplified by those developed by BioNTech/Pfizer and Moderna against COVID-19, have gained approval for human use. This review highlights rational design strategies for vaccine delivery, emphasizing lymphoid organ targeting and effective endosomal escape. It also discusses the importance of rational formulation design and structure–activity relationships, along with reviewing components and potential applications of lipid-based vectors. Additionally, it addresses current challenges and future prospects in translating lipid-based vaccine therapies for cancer and infectious diseases into clinical practice. Full article
(This article belongs to the Special Issue mRNA Vaccines: Pioneering the Future of Vaccination)
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