Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques DOI Creative Commons
Lulu Huang,

Tongyi Zhao,

Weijun Zhao

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 23, 2024

Herpes zoster remains an important global health issue and mainly occurs in aged immunocompromised individuals with early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has a remarkably high efficacy, undesired reactogenicity increasing demand causing shortage urged development of improved or novel VZV vaccines. In this study, we developed mRNA candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated ionizable lipid nanoparticle. mice rhesus macaques, ZOSAL demonstrated superior immunogenicity safety multiple aspects over Shingrix, especially induction strong T cell immunity. Transcriptomic analysis revealed that both could robustly activate innate immune compartments, Type-I IFN signaling antigen processing/presentation. Multivariate correlation further identified several factors compartments can predict magnitude responses, which increased our understanding mode action two different modalities. Collectively, data superiority subunit vaccine. The platform therefore holds prospects for investigations next-generation development.

Language: Английский

Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment DOI Creative Commons
Yujing Huang, Xiaohan Guo, Yi Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 21, 2024

Abstract Inflammation-associated diseases encompass a range of infectious and non-infectious inflammatory diseases, which continuously pose one the most serious threats to human health, attributed factors such as emergence new pathogens, increasing drug resistance, changes in living environments lifestyles, aging population. Despite rapid advancements mechanistic research development for these current treatments often have limited efficacy notable side effects, necessitating more effective targeted anti-inflammatory therapies. In recent years, nanotechnology has provided crucial technological support prevention, treatment, detection inflammation-associated diseases. Various types nanoparticles (NPs) play significant roles, serving vaccine vehicles enhance immunogenicity carriers improve targeting bioavailability. NPs can also directly combat pathogens inflammation. addition, facilitated biosensors pathogen imaging techniques This review categorizes characterizes different NPs, summarizes their applications It discusses challenges associated with clinical translation this field explores latest developments prospects. conclusion, opens up possibilities comprehensive management

Language: Английский

Citations

141
Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability DOI Creative Commons
Lizhou Zhang, Kunal R. More, Amrita Ojha

et al.

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 11, 2023

Abstract During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components distinct. Here, we compared effect of ionizable lipids, untranslated regions (UTRs), nucleotide composition two vaccines, focusing on delivery, antibody generation, long-term stability. We found that lipid, SM-102, Moderna’s vaccine performs better than ALC-0315 Pfizer-BioNTech’s for intramuscular delivery production mice stability at 4 °C. Moreover, 5′ UTR 3′ outperform their counterparts contribution to transgene expression mice. further varying N1-methylpseudouridine content wobble position has little efficacy. These findings may contribute improvement mRNA-LNP therapeutics.

Language: Английский

Citations

81
Recent Advances in the Lipid Nanoparticle-Mediated Delivery of mRNA Vaccines DOI Creative Commons
K. Swetha, Niranjan G. Kotla, Lakshmi Tunki

et al.

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 658 - 658

Published: March 14, 2023

Lipid nanoparticles (LNPs) have recently emerged as one of the most advanced technologies for highly efficient in vivo delivery exogenous mRNA, particularly COVID-19 vaccine delivery. LNPs comprise four different lipids: ionizable lipids, helper or neutral cholesterol, and lipids attached to polyethylene glycol (PEG). In this review, we present recent advances insights design LNPs, well their composition properties, with a subsequent discussion on development vaccines. particular, are critical drivers complexing mRNA delivery, role vaccines is discussed detail. Furthermore, use effective vehicles vaccination, genome editing, protein replacement therapy explained. Finally, expert opinion discussed, which may address future challenges developing using based novel set lipids. Developing systems improved safety against some severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains difficult.

Language: Английский

Citations

63
Strategies to reduce the risks of mRNA drug and vaccine toxicity DOI
Dimitrios Bitounis, Eric Jacquinet, Maximillian A. Rogers

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(4), P. 281 - 300

Published: Jan. 23, 2024

Language: Английский

Citations

63
Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity DOI Creative Commons
Liusheng Wu, Xiaoqiang Li,

Xinye Qian

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 186 - 186

Published: Feb. 12, 2024

In recent years, lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy. Targeting immune cells cancer therapy has become a strategy of great research interest. mRNA vaccines are potential choice for immunotherapy, due to their ability directly encode antigen proteins and stimulate strong response. However, the mode delivery lack stability key issues limiting its application. LNPs an excellent carrier, structural biocompatibility make them effective means delivering specific targets. This study summarizes progress LNP carrier-assisted targeted controlled release immunity. The role improving stability, immunogenicity, targeting is discussed. review aims systematically summarize latest immunity provide new ideas strategies as well more treatment plans patients.

Language: Английский

Citations

53
From structural design to delivery: mRNA therapeutics for cancer immunotherapy DOI Creative Commons
Feng Zhou, Lujia Huang,

Shiqin Li

et al.

Exploration, Journal Year: 2023, Volume and Issue: 4(2)

Published: Nov. 17, 2023

Abstract mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority expressing all sequence‐known proteins vivo. In particular, a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens present epitopes to T lymphocytes elicit antitumor effects. addition, receptors like chimeric antigen receptor (CAR), T‐cell (TCR), CD134, immune‐modulating factors including cytokines, interferons, antibodies specific enhance immunological response against tumors. With the maturation vitro transcription (IVT) technology, large‐scale pure encoding be synthesized quickly. However, clinical translation mRNA‐based anticancer strategies is restricted by delivering into target organs or inadequate endosomal escape efficiency mRNA. Recently, there been some advances immunotherapy, which roughly classified modifications structure development delivery systems, especially lipid nanoparticle platforms. this review, latest overcoming limitations immunotherapies recent are summarized. Challenges opportunities applications also discussed.

Language: Английский

Citations

50
Chemically Modified Platforms for Better RNA Therapeutics DOI

Yesi Shi,

Xueyan Zhen,

Yiming Zhang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(3), P. 929 - 1033

Published: Jan. 29, 2024

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential disease prevention and treatment. However, despite their remarkable achievements, these encounter substantial challenges including low stability, susceptibility to degradation by nucleases, prominent negative charge, thereby hindering further development. Chemically modified platforms emerged as strategic innovation, focusing on precise alterations either RNA moieties or associated delivery vectors. This comprehensive review delves into platforms, underscoring significance augmenting performance translational prospects of therapeutics. It encompasses an in-depth analysis various chemically that been instrumental propelling therapeutics toward clinical utility. Moreover, scrutinizes rationale behind diverse chemical modification techniques aiming at optimizing therapeutic efficacy molecules, facilitating robust management. Recent empirical studies corroborating enhancement through modifications are highlighted. Conclusively, we offer profound insights transformative impact drugs delineates prospective trajectories for future development integration.

Language: Английский

Citations

46
Recent advances in nanoparticulate RNA delivery systems DOI Creative Commons
Jacob Witten, Yizong Hu, Róbert Langer

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(11)

Published: March 4, 2024

Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss preclinical clinical advancement new generations therapies along multiple axes. Improvements cargo design such as circularization data-driven untranslated region optimization can drive better expression. New materials discovery research driven improved to extrahepatic targets lung splenic immune cells, which could lead pulmonary gene therapy cancer vaccines, respectively. Other organs even specific cell types be targeted via conjugation small molecule ligands, antibodies, or peptides nanoparticles. Moreover, response any nanoparticle plays crucial role determining efficacy. Targeting increased immunogenicity without induction reactogenic side effects is while minimization important therapies. developments have addressed each these priorities. Last, range trials targeting diverse organs, types, diseases suggest some key advances that may play next wave

Language: Английский

Citations

36
PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge DOI Creative Commons
Yongxiang Zhao, Baochao Fan,

Xu Song

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(2)

Published: Jan. 17, 2024

Porcine epidemic diarrhea virus (PEDV) continues to harm the global swine industry. It is important develop a highly effective vaccine control PEDV infection. Here, we report spike (S) mRNA that primes potent antibody response and antigen-specific T-cell responses in immunized piglets. Active passive immunization can protect piglets against PED following challenge. This study highlights efficiency of PEDV-S represents viable approach for developing an efficient vaccine.

Language: Английский

Citations

27
Myocarditis associated with COVID-19 vaccination DOI Creative Commons
Alessandra Buoninfante, Arno C. Andeweg, Georgy Genov

et al.

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 28, 2024

Following the start of COVID-19 vaccination campaign, adverse events myocarditis and pericarditis were linked mainly to mRNA vaccines by regulatory authorities worldwide. have been administered several million people risk post has characterised in great detail. At present time research data available are scarce there is still no clear understanding biological mechanism/s responsible for this disease. This manuscript provides a concise overview epidemiology most prominent mechanistic insights pathophysiology Most importantly it underscores needed next steps agenda required characterize disease post-COVID-19 vaccination. Finally, shares our perspectives considerations public health.

Language: Английский

Citations

20