Modelling the Relative Vaccine Efficacy of ARCT-154, a Self-Amplifying mRNA COVID-19 Vaccine, versus BNT162b2 Using Immunogenicity Data DOI Creative Commons
Văn Hùng Nguyễn, Pascal Crépey,

Jean Marie Pivette

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(10), P. 1161 - 1161

Published: Oct. 11, 2024

Background: Self-amplifying mRNA vaccines have the potential to increase magnitude and duration of protection against COVID-19 by boosting neutralizing antibody titers cellular responses. Methods: In this study, we used immunogenicity data from a phase 3 randomized trial comparing ARCT-154, self-amplifying vaccine, with BNT162b2 vaccine estimate relative efficacy (rVE) two over time in younger (<60 years) older (≥60 adults. Results: By day 181 post-vaccination, rVE symptomatic severe Wuhan-Hu-1 disease was 9.2–11.0% 1.2–1.5%, respectively, across age groups whereas Omicron BA.4/5 26.8–48.0% 5.2–9.3%, groups. Sensitivity analysis showed that varying threshold titer for 50% up 10% convalescent sera revealed incremental benefits ARCT-154 BNT162b2, an 28.0% adults aged ≥60 year. Conclusions: Overall, results study indicate elicits broader more durable SARS-CoV-2, translating enhanced protection, particularly BA.4/5.

Language: Английский

Differential clearance rate of proteins encoded on a self-amplifying mRNA COVID-19 vaccine in muscle and lymph nodes DOI

Reo Kanechi,

Tatsuya Shishido,

Mana Tachikawa

et al.

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 42, P. 101999 - 101999

Published: April 5, 2025

Language: Английский

Citations

0
Safety profile of self-amplifying mRNA SARS-CoV-2 vaccine ARCT-154 in adults: a pooled phase 1/2/3 randomized clinical study DOI Creative Commons
Nhan Thi Ho, Igor Smolenov,

Lydia Tran

et al.

Expert Review of Vaccines, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Public health concerns due to ongoing emergence of SARS-CoV-2 variants necessitates further development improved COVID-19 vaccines. One major innovation are self-amplifying mRNA vaccines such as ARCT-154 (Arcturus Therapeutics Inc.) which induces superior immunogenicity compared with conventional in terms magnitude, breadth and persistence neutralizing antibodies. In a pivotal placebo-controlled trial Vietnam combining phase 1, 2 3 cohorts, over 17,000 adults received at least one dose ARCT-154. Here we report the safety reactogenicity observations made. elicited more local reactions than saline placebo, most reports injection site pain were mild/moderate only few reporting severe pain. Most frequent solicited adverse events fatigue, myalgia, headache, arthralgia chills. Solicited systemic resolved within 7 days. Long-term follow-up has not revealed any concerns, no myocarditis or pericarditis. Acceptable tolerability was also observed older participants those liable consequences underlying medical conditions. No serious occurred several pregnancies reported after vaccination, normal outcomes when followed term. Data from this large suggest that is safe well tolerated.

Language: Английский

Citations

0
Self-Amplifying RNA: Advantages and Challenges of a Versatile Platform for Vaccine Development DOI Creative Commons
Thomas Vallet,

Marco Vignuzzi

Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 566 - 566

Published: April 14, 2025

Self-amplifying RNA is synthetic nucleic acid engineered to replicate within cells without generating viral particles. Derived from alphavirus genomes, saRNA retains the non-structural elements essential for replication while replacing structural with an antigen of interest. By enabling efficient intracellular amplification, offers a promising alternative conventional mRNA vaccines, enhancing expression requiring lower doses. However, this advantage comes challenges. In review, we highlight key limitations technology and explore potential strategies overcome them. identifying these challenges, aim provide insights that can guide future design saRNA-based therapeutics, extending their beyond vaccine applications.

Language: Английский

Citations

0
Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern DOI Creative Commons
Ankita Saha, Sounak Ghosh Roy, Richa Dwivedi

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 424 - 424

Published: April 17, 2025

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating severity clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have developed to this effect, including BioNTech-Pfizer Moderna’s mRNA vaccines, as well adenovirus vector-based such Oxford–AstraZeneca. However, emergence new variants subvariants SARS-CoV-2, characterized by enhanced transmissibility immune evasion, poses significant challenges efficacy current vaccination strategies. In review, we aim comprehensively outline landscape emerging concern (VOCs) sub-lineages that recently surfaced post-pandemic years. We assess effectiveness existing their booster doses, against these subvariants, BA.2-derived sub-lineages, XBB BA.2.86 (Pirola). Furthermore, discuss latest advancements vaccine technology, multivalent pan-coronavirus approaches, along development several next-generation coronavirus exosome-based, virus-like particle (VLP), mucosal, nanomaterial-based vaccines. Finally, highlight key critical areas for future research address evolving threat develop strategies combating viral threats, thereby improving preparedness pandemics.

Language: Английский

Citations

0
Synthetic mRNAs Containing Minimalistic Untranslated Regions Are Highly Functional In Vitro and In Vivo DOI Creative Commons

Shahab Mamaghani,

Rocco Roberto Penna, Julia Frei

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1242 - 1242

Published: July 24, 2024

Synthetic mRNA produced by in vitro transcription (ivt mRNA) is the active pharmaceutical ingredient of approved anti-COVID-19 vaccines and many drugs under development. Such synthetic typically contains several hundred bases non-coding “untranslated” regions (UTRs) that are involved stabilization translation mRNA. However, UTRs often complex structures, which may complicate entire production process. To eliminate this obstacle, we managed to reduce total amount nucleotides only four bases. In way, generate minimal ivt (“minRNA”), less than usual optimized mRNAs contained, for example, vaccines. We have compared efficacy minRNA common augmented (with globin genes or those included licensed vaccines) vivo could demonstrate equivalent functionalities. Our design will facilitate further development implementation mRNA-based therapies.

Language: Английский

Citations

3
Cytokine Storms and Anaphylaxis Following COVID-19 mRNA-LNP Vaccination: Mechanisms and Therapeutic Approaches DOI Creative Commons
Toru Awaya, Hidehiko Hara, Masao Moroi

et al.

Diseases, Journal Year: 2024, Volume and Issue: 12(10), P. 231 - 231

Published: Oct. 1, 2024

Acute adverse reactions to COVID-19 mRNA vaccines are a major concern, as autopsy reports indicate that deaths most commonly occur on the same day of or one following vaccination. These acute may be due cytokine storms triggered by lipid nanoparticles (LNPs) and anaphylaxis induced polyethene glycol (PEG), both which vital constituents mRNA-LNP vaccines. Kounis syndrome, in triggers coronary syndrome (ACS), also responsible for these cardiovascular events. Furthermore, encompass adjuvants, such LNPs, trigger inflammatory cytokines, including interleukin (IL)-1β IL-6. produce spike proteins facilitate release cytokines. Apart from this, histamine released mast cells during allergic plays critical role IL-6 secretion, intensifies responses. In light events, early reduction IL-1β is imperative managing post-vaccine storms, ACS, myocarditis. Corticosteroids can restrict cytokines mitigate responses, while colchicine, known its IL-1β-reducing capabilities, could prove effective. The anti-IL-6 antibody tocilizumab displays promising treatment syndrome. Aside significance treating anaphylaxis, epinephrine induce artery spasms myocardial ischemia making accurate diagnosis essential. upcoming self-amplifying contain LNPs. Given cause storm post vaccination, it crucial consider corticosteroids measure levels effective management.

Language: Английский

Citations

3
The role of helper lipids in optimising nanoparticle formulations of self-amplifying RNA DOI Creative Commons
Beatriz Dias Barbieri, David J. Peeler, Karnyart Samnuan

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 374, P. 280 - 292

Published: Aug. 22, 2024

Lipid nanoparticle (LNP) formulation plays a vital role in RNA vaccine delivery. However, further optimisation of self-amplifying (saRNA) could help enhance seroconversion rates humans and improve storage stability. Altering either the ionisable or helper lipid can alter characteristics performance formulated saRNA through interplay phospholipid's packing parameter geometrical shape within LNP membrane. In this study, we compared impact three lipids (DSPC, DOPC, DOPE) used with two different (MC3 C12-200) on stability, transfection efficiency inflammation immunogenicity saRNA. While identity altered expression across four cell lines vitro, was not predictive an ex vivo response. The influenced where DSPC provided best stability profile over weeks at 2-8 °C. Importantly, predictor human skin explants, C12-200 combination most durable expression. LNPs also improved protein (firefly luciferase) humoral responses to SARS-CoV-2 spike MC3 LNPs, effect less apparent. Nevertheless, appears optimal for when balancing preferred requirements against potency. These data suggest that influences functionality nanoparticle-formulated

Language: Английский

Citations

2
RNA technology and nanocarriers empowering in vivo chimeric antigen receptor therapy DOI

Jingsheng Cai,

Shaoyi Chen,

Zheng Liu

et al.

Immunology, Journal Year: 2024, Volume and Issue: 173(4), P. 634 - 653

Published: Sept. 28, 2024

Abstract The remarkable success of mRNA‐based coronavirus 2019 (COVID‐19) vaccines has propelled the advancement nanomedicine, specifically in realm RNA technology and nanomaterial delivery systems. Notably, significant strides have been made development RNA‐based vivo chimeric antigen receptor (CAR) therapy. In comparison to conventional ex CAR therapy, therapy offers several benefits including simplified preparation, reduced costs, broad applicability decreased potential for carcinogenic effects. This review summarises constructs discusses current applications vectors outlines immune cells edited with molecules. We aim conveyed messages contribute towards application.

Language: Английский

Citations

2
Immunogenicity of a booster dose of a bivalent (Asp614Gly and omicron BA.4/5 variant) self-amplifying mRNA SARS-CoV-2 booster vaccine versus the BNT162b2 omicron BA.4/5 mRNA vaccine: a randomised phase 3 trial DOI
Yusuke Okada,

Yuji Kumagai,

Iori Okura

et al.

The Lancet Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

2
Bridging gene therapy and next-generation vaccine technologies DOI Creative Commons
Kristie Bloom, Abdullah Ely, Mohube Betty Maepa

et al.

Gene Therapy, Journal Year: 2024, Volume and Issue: 32(1), P. 4 - 7

Published: Nov. 18, 2024

Language: Английский

Citations

2