Spleen-selective co-delivery of mRNA and TLR4 agonist-loaded LNPs for synergistic immunostimulation and Th1 immune responses

Pan, Longze; Zhang, Lijing; Deng, Wei; Jia, Lixin; Gao, Xiaoke; Lou, Xiaohan; Liu, Yangyang; Yao, Xiaohan; Sheng, Yuchen; Yan, Yan; Chen, Ni; Wang, Ming; Tian, Chuntao; Wang, Fazhan; Qin, Zhihai

doi:10.1016/j.jconrel.2023.03.041

Cited by 35 publications

(17 citation statements)

References 52 publications

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“…This can be observed from Figure , where the LNPs reaching the spleen did not produce a Luciferase signal as strong as in other organs (i.e., liver). Efficient spleen targeting in vaccines can improve immune responses, including increased antibody production, enhanced cellular immunity, and prolonged antigen presentation. , …”

Section: Discussionmentioning

confidence: 99%

Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Mancino,

Pollet,

Zinger

et al. 2024

ACS Appl. Mater. Interfaces

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Chagas disease (CD) (American trypanosomiasis caused by Trypanosoma cruzi) is a parasitic disease endemic in 21 countries in South America, with increasing global spread. When administered late in the infection, the current antiparasitic drugs do not prevent the onset of cardiac illness leading to chronic Chagasic cardiomyopathy. Therefore, new therapeutic vaccines or immunotherapies are under development using multiple platforms. In this study, we assessed the feasibility of developing an mRNA-based therapeutic CD vaccine targeting two known T. cruzi vaccine antigens (Tc24�a flagellar antigen and ASP-2�an amastigote antigen). We present the mRNA engineering steps, preparation, and stability of the lipid nanoparticles and evaluation of their uptake by dendritic cells, as well as their biodistribution in c57BL/J mice. Furthermore, we assessed the immunogenicity and efficacy of two mRNA-based candidates as monovalent and bivalent vaccine strategies using an in vivo chronic mouse model of CD. Our results show several therapeutic benefits, including reductions in parasite burdens and cardiac inflammation, with each mRNA antigen, especially with the mRNA encoding Tc24, and Tc24 in combination with ASP-2. Therefore, our findings demonstrate the potential of mRNA-based vaccines as a therapeutic option for CD and highlight the opportunities for developing multivalent vaccines using this approach.

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Section: Discussionmentioning

confidence: 99%

Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Mancino,

Pollet,

Zinger

et al. 2024

ACS Appl. Mater. Interfaces

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show abstract

“…For instance, Pan et al designed a novel nanovaccine to deliver OVA mRNA and TLR agonists into the spleen after IV administration, resulting in a sufficient and persistent anti-tumor cellular immune response. [123] Gu et al developed a spleen-targeted polymersome as nanovaccine to dramatically boost splenic immune responses in both acute myeloid leukemia, melanoma, and lung metastasis mouse models. [124] We expect to see these innovative formulations for both prophylactic and therapeutic vaccines be approved for clinical applications soon.…”

Section: Discussionmentioning

confidence: 99%

Recent Advances of Emerging Spleen‐Targeting Nanovaccines for Immunotherapy

Wang

Tang

et al. 2023

Adv Healthcare Materials

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Vaccines provide a powerful tool to modulate the immune system for human disease prevention and treatment. Classical vaccines mainly initiate immune responses in the lymph nodes (LNs) after subcutaneous injection. However, some vaccines suffer from inefficient delivery of antigens to LNs, undesired inflammation, and slow immune induction when encountering the rapid proliferation of tumors. Alternatively, the spleen, as the largest secondary lymphoid organ with a high density of antigen‐presenting cells (APCs) and lymphocytes, acts as an emerging target organ for vaccinations in the body. Upon intravenous administration, the rationally designed spleen‐targeting nanovaccines can be internalized by the APCs in the spleen to induce selective antigen presentation to T and B cells in their specific sub‐regions, thereby rapidly boosting durable cellular and humoral immunity. Herein, the recent advances of spleen‐targeting nanovaccines for immunotherapy based on the anatomical architectures and functional zones of the spleen, as well as their limitations and perspectives for clinical applications are systematically summarized. The aim is to emphasize the design of innovative nanovaccines for enhanced immunotherapy of intractable diseases in the future.

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“… 69 Furthermore, mRNA-LNPs containing stearic acid as an additive, a well-studied compound in the realm of drug delivery, 70 were found to selectively express mRNA in the spleen following intravenous injections. 71 In addition, Daniel J. Siegwart and colleagues proved by SORT technology that anionic SORT lipids, specifically 1,2-dimyristoyl- sn -glycero-3-phosphate (sodium salt) (14PA) and sn-(3-oleoyl-2-hydroxy)-glycerol-1-phospho- sn -3’-(1′,2′-dioleoyl)-glycerol (ammonium salt) (18BMP), promoted the selective delivery of LNPs to the spleen, with 30% 1,2-dioleoyl- sn -glycero-3-phosphate (18PA) SORT LNPs demonstrating spleen-targeting potential during trials 42 …”

Section: Organ-selective Lnps As Delivery Platforms For Nucleic Acidsmentioning

confidence: 99%

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Zhang,

Yin,

et al. 2024

iScience

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Spleen-selective co-delivery of mRNA and TLR4 agonist-loaded LNPs for synergistic immunostimulation and Th1 immune responses

Cited by 35 publications

References 52 publications

Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Recent Advances of Emerging Spleen‐Targeting Nanovaccines for Immunotherapy

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

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