Cationic lipids as one-component vaccine adjuvants: A promising alternative to alum

Pizzuto, Malvina; Bigey, Pascal; Lachagès, Anne-Marie; Hoffmann, Céline; Ruysschaert, Jean Marie; Escriou, Virginie; Lonez, Caroline

doi:10.1016/j.jconrel.2018.08.020

Cited by 35 publications

(50 citation statements)

References 45 publications

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“…The brief P2X7 receptor activation in resting macrophages with millimolar concentrations of ATP used in this study did not compromise cell viability and may resemble physiological conditions where ectonucleotidases provoke a fast ATP degradation in the extracellular milieu (Eltzschig et al, 2012). Under these conditions, there is a reduction in the subsequent production of pro-inflammatory cytokines after a smooth LPS activation that requires CD14 to signal via the TLR4-MD2 complex (Pizzuto et al, 2018;Ryu et al, 2017). This suggests that the release of CD14 from macrophages impairs CD14 signaling, and probably also the translocation of TLR4 complex to endosomes, thus impairing TRAM-TRIF-dependent pathways (Zanoni et al, 2013).…”

Section: Discussionmentioning

confidence: 90%

“…This effect was abrogated when the specific P2X7 receptor antagonist A438079 was used or when macrophages were isolated from P2rx7 −/− mice (Figure 2a,b), thus suggesting that the P2X7 receptor was affecting LPS signaling in macrophages. LPS is not able to activate TLR4 in the absence of CD14 at the cell membrane (Pizzuto et al, 2018). By contrast, lipopolysaccharides with smaller hydrophilic moiety, like monophosphoryl lipid A (MPLA), signals independently of CD14 (Maeshima and Fernandez, 2013).…”

Section: P2x7 Receptor Stimulation Impairs Lps-mediated Signalingmentioning

confidence: 99%

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CD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis

Alarcón‐Vila

Baroja‐Mazo

Torre‐Minguela

et al. 2020

eLife

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P2X7 receptor activation induces the release of different cellular proteins, such as CD14, a glycosylphosphatidylinositol (GPI)-anchored protein to the plasma membrane important for LPS signaling via TLR4. Circulating CD14 has been found at elevated levels in sepsis, but the exact mechanism of CD14 release in sepsis has not been established. Here we show for first time that P2X7 receptor induces the release of CD14 in extracellular vesicles, resulting in a net reduction in macrophage plasma membrane CD14 that functionally affects LPS, but not monophosphoryl lipid A, pro-inflammatory cytokine production. Also, we found that during a murine model of sepsis, P2X7 receptor activity is important for maintaining elevated levels of CD14 in biological fluids and a decrease in its activity results in higher bacterial load and exacerbated organ damage, ultimately leading to premature deaths. Our data reveal that P2X7 is a key receptor for helping to clear sepsis because it maintains elevated concentrations of circulating CD14 during infection.

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Section: Discussionmentioning

confidence: 90%

Section: P2x7 Receptor Stimulation Impairs Lps-mediated Signalingmentioning

confidence: 99%

CD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis

Alarcón‐Vila

Baroja‐Mazo

Torre‐Minguela

et al. 2020

eLife

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“… 109 Full-length mRNA encoding multiple antigen targets plus appropriate delivery systems might be a promising approach. Lipid/polymer nanocarriers, such as cationic lipopolyamines, 110 polyglycolic- co -lactides, chitosan, and polymersomes, 111 are proven to act as adjuvants. Lipids derived from bacteria or those containing synthetic α-lipo-amino acids can act as TLR agonists that could recognize structural proteins of viruses.…”

Section: Current Status Of Sars-cov-2 Vaccine Developmentmentioning

confidence: 99%

SARS-CoV-2 Vaccine Development: An Overview and Perspectives

Liu

Wang

Massoud

et al. 2020

ACS Pharmacol. Transl. Sci.

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Coronavirus disease 2019, abbreviated as COVID-19, is caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It started in late December 2019 in Wuhan, China, and by mid-March 2020, the disease had spread globally. As of July 17, 2020, this pandemic virus has infected 13.9 million people and claimed the life of approximately 593 000 people globally, and the numbers continue to climb. An unprecedented effort is underway to develop therapeutic and prophylactic strategies against this disease. Various drugs and vaccines are undergoing rapid development, and some of these are already in phase III clinical trials. Although Russia was the first to release a vaccine by skipping phase III clinical trials, there is no evidence of large-scale clinical trials, and the safety and efficacy of the vaccine are still a concern. Nevertheless, critical lessons can be learned and data garnered for developing promising vaccines against this rapidly emerging virus or other similar pathogens in the future. In this overview, we cover the available information on the various vaccine development initiatives by different companies, the potential strategies adopted for vaccine design, and the challenges and clinical impact expected from these vaccines. We also briefly discuss the possible role of these vaccines and the specific concerns for their use in patients with pre-existing disease conditions such as cardiovascular, lung, kidney, and liver diseases, cancer patients who are receiving immunosuppressive medications, including anticancer chemotherapies, and many other sensitive populations, such as children and the elderly.

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“…A particularly interesting class of cationic lipids is the lipopolyamines synthesized by Byk and coworkers in the 1990s aiming at DNA transfer to cells [ 69 ]. They were recently explored by Pizzuto and coworkers as single-component adjuvants able to elicit both Th1 and Th2 responses in absence of toxicity in vivo [ 70 ]. Figure 3 illustrates the ability of these polyamines to activate Toll-like receptor 2 (TLR2) and 4 (TLR4) besides inducing, in combination with OVA antigen, both IgG1 and IgG2a; OVA alone or Alum induced exclusively IgG1, and lipopolyamines induced both IgG1 and IgG2a antibodies production [ 70 ].…”

Section: Assemblies From Cationic Lipids and Surfactantsmentioning

confidence: 99%

Cationic Nanostructures for Vaccines Design

Carmona-Ribeiro

Betancourt

2020

Biomimetics

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Subunit vaccines rely on adjuvants carrying one or a few molecular antigens from the pathogen in order to guarantee an improved immune response. However, to be effective, the vaccine formulation usually consists of several components: an antigen carrier, the antigen, a stimulator of cellular immunity such as a Toll-like Receptors (TLRs) ligand, and a stimulator of humoral response such as an inflammasome activator. Most antigens are negatively charged and combine well with oppositely charged adjuvants. This explains the paramount importance of studying a variety of cationic supramolecular assemblies aiming at the optimal activity in vivo associated with adjuvant simplicity, positive charge, nanometric size, and colloidal stability. In this review, we discuss the use of several antigen/adjuvant cationic combinations. The discussion involves antigen assembled to 1) cationic lipids, 2) cationic polymers, 3) cationic lipid/polymer nanostructures, and 4) cationic polymer/biocompatible polymer nanostructures. Some of these cationic assemblies revealed good yet poorly explored perspectives as general adjuvants for vaccine design.

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Cationic lipids as one-component vaccine adjuvants: A promising alternative to alum

Cited by 35 publications

References 45 publications

CD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis

CD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis

SARS-CoV-2 Vaccine Development: An Overview and Perspectives

Cationic Nanostructures for Vaccines Design

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