Lipopolyplex-formulated mRNA cancer vaccine elicits strong neoantigen-specific T cell responses and antitumor activity

Science Advances, Journal Year: 2024, Volume and Issue: 10(41)

Published: Oct. 11, 2024

mRNA neoantigen cancer vaccine inducing neoantigen-specific T cell responses holds great promise for immunotherapy; however, its clinical translation remains challenging because of suboptimal prediction accuracy and low delivery efficiency, which compromise the in vivo therapeutic efficacy. We present a lipopolyplex (LPP)–formulated encoding tandem neoantigens as regimen. The LPP-formulated vaccines elicited robust CD8 + three syngeneic murine tumor models (CT26, MC38, B16F10) to suppress growth. Prophylactic treatment completely prevented development, long-lasting memory cells protected mice from rechallenge. Combining with immune checkpoint inhibitor further boosted antitumor activity. Of note, LPP-based personalized was administered two patients induced meaningful responses. In conclusion, we demonstrated that can elicit strong responses, results support evaluation vaccine.

Language: Английский

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Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus

Vaccines, Journal Year: 2025, Volume and Issue: 13(1), P. 93 - 93

Published: Jan. 20, 2025

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and children. mRNA vaccines based on lipopolyplex (LPP) platform have been previously reported, but they remain unapplied RSV vaccine development. In this study, we developed a novel LPP-delivered that expresses prefusion protein (RSV pre-F) to evaluate its immunogenicity protective effect mouse model. We synthesized mRNAs with gene modification for pre-F prepared using LPP delivery platform, referred as LPP-mRNA. expression was characterized vitro. Then, evaluated effects immune response protection mice up 24 weeks post-vaccination. Following booster immunization, robust long-lasting pre-F-specific IgG antibodies were detected serum mice, which exhibited Th1/Th2 balanced cross-neutralizing against different subtypes A2, B18537, clinical isolate hRSV/C-Tan/BJ 202301), clear dose–response relationship observed. maintained an extended period, lasting 18 post-immunization. Concurrently, multifunctional F-specific CD8+ T cells (IFN–γ, IL-2, TNF-α) mice. After A2 challenge, LPP-mRNA led significant reduction viral replication, while reduced pathological damage observed lung tissue. The expressing induces protection, indicating good prospects further development application.

Language: Английский

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Influence of salt solution on the physicochemical properties and in vitro/ in vivo expression of mRNA/LNP

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 19, 2025

Lipid nanoparticles (LNPs) have revolutionized nucleic acid delivery, enabling significant advances in mRNA-based therapeutics. While extensive research has focused on lipid composition, the impact of preparation solutions LNP performance remains underexplored. This study systematically investigated effects pH, salt type, and concentration across key solutions—mRNA aqueous, dilution, exchange, storage solutions—on physicochemical properties, stability, expression efficiency SM102-based mRNA/LNPs. Findings revealed that pH mRNA aqueous solution was critical, with a 4 optimizing encapsulation (EE) cellular expression. The exchange solution's significantly influenced biodistribution, particularly liver-specific following intravenous intramuscular administration. Sucrose identified as essential for freeze-thaw 300 mM minimizing aggregation leakage. Furthermore, were shown to influence structural integrity LNPs, impacting their vivo vitro performance. These insights highlight importance conditions formulations clinical applications, offering foundation enhanced therapeutic design delivery.

Language: Английский

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Biocompatible lipid nanovehicles for preventive and therapeutic vaccine development

Coordination Chemistry Reviews, Journal Year: 2025, Volume and Issue: 538, P. 216718 - 216718

Published: April 22, 2025

Language: Английский

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Broad-spectrum Delta-BA.2 tandem-fused heterodimer mRNA vaccine delivered by lipopolyplex

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(4), P. e1012116 - e1012116

Published: April 1, 2024

Since the beginning of coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome 2 (SARS-CoV-2), causative agent COVID-19, continues to mutate and generates new variants with increasingly immune escape, urging upgrade COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed novel broad-spectrum mRNA SWIM516, chimeric Delta-BA.2 dimer delivered by lipopolyplex (LPP). Unlike popular lipid nanoparticle (LNP), this LPP-delivered expresses only in injection site, which avoids potential toxicity liver. We demonstrated humoral cellular immunogenicity vaccine Delta Omicron sub-variants naïve mice booster shots. When challenged or live virus, vaccinated human angiotensin-converting enzyme (hACE2) transgenic rhesus macaques were both protected, displaying significantly reduced viral loads markedly relieved pathological damages. believe SWIM516 qualifies candidate for next-generation vaccine.

Language: Английский

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Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 373, P. 837 - 852

Published: Aug. 3, 2024

Language: Английский

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