Thermoresponsive Polymer Nanoparticles Co-deliver RSV F Trimers with a TLR-7/8 Adjuvant

Francica, Joseph R.; Lynn, Geoffrey M.; Laga, Richard; Joyce, Michael; Ruckwardt, Tracy J.; Morabito, Kaitlyn M.; Chen, Man; Chaudhuri, Rajoshi; Zhang, Baoshan; Sastry, Mallika; Druz, Aliaksandr; Ko, Kiyoon; Choe, Misook; Pechar, Michal; Georgiev, Ivelin S.; Kueltzo, Lisa A.; Seymour, Leonard W.; Mascola, John R.; Kwong, Peter D.; Graham, Barney S.; Seder, Robert A.

doi:10.1021/acs.bioconjchem.6b00370

Cited by 46 publications

(33 citation statements)

References 86 publications

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“…Recently, thermo-responsive synthetic polymers (TRP) nanoparticles based on the N-isopropylacrylamide (NIPAM), and N-(2-hydroxypropyl) methacrylamide (HPMA) polymers, which are able to selfassemble into immunogenic particles at physiologic temperatures, have been developed for the co-delivery of toll like receptor 7 and 8 agonists (TLR-7/8a) as adjuvants and immunogens such as respiratory syncytial virus (RSV) fusion (F) protein trimers. TRP nanoparticles induce broadbased humoral and cellular immune responses; moreover, they are stable, soluble, filterable, colloidally dispersed, and unimolecular during purification and storage phases (Francica et al, 2016;Lynn et al, 2015). Currently, various vaccines based on polymeric nanoparticles are being tested in pre-clinical and clinical trials as treatments for different diseases, such as human immunodeficiency virus (HIV), cancer, and tuberculosis (Bolhassani et al, 2014) (Table 1).…”

Section: Polymeric Nanoparticlesmentioning

confidence: 99%

Harnessing self-assembled peptide nanoparticles in epitope vaccine design

Negahdaripour

Golkar

Hajighahramani

et al. 2017

Biotechnology Advances

103

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Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility. They also resemble pathogens in terms of their size. Their multivalency allows an orderly repetitive display of antigens on their surface, which induces a stronger immune response than single immunogens. In vaccine design, SAPN self-adjuvanticity is regarded an outstanding advantage, since the use of toxic adjuvants is no longer required. SAPNs are usually composed of helical or β-sheet secondary structures and are tailored from natural peptides or de novo structures. Flexibility in subunit selection opens the door to a wide variety of molecules with different characteristics. SAPN engineering is an emerging area, and more novel structures are expected to be generated in the future, particularly with the rapid progress in related computational tools. The aim of this review is to provide a state-of-the-art overview of self-assembled peptide nanoparticles and their use in vaccine design in recent studies. Additionally, principles for their design and the application of computational approaches to vaccine design are summarized.

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Section: Polymeric Nanoparticlesmentioning

confidence: 99%

Harnessing self-assembled peptide nanoparticles in epitope vaccine design

Negahdaripour

Golkar

Hajighahramani

et al. 2017

Biotechnology Advances

103

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“…The nanoparticle-TLR formulation, in comparison to alum adjuvant, significantly enhanced the magnitude and persistence of antigen-specific antibody responses. Francica and Seder (31,32) have designed thermo-responsive polymer nanoparticles to co-deliver pathogen antigens. This platform holds promise for structure-based vaccine designs potentially including HIV-1 Env neutralizing epitopes.…”

Section: Recent Preclinical Investigations With Hiv Vaccine-adjuvant mentioning

confidence: 99%

Adjuvants

McElrath

2017

Current Opinion in HIV and AIDS

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Purpose of review The development and availability of new generation adjuvants beyond aluminum and emulsion formulations, together with a deeper understanding of the mechanistic role of adjuvant formulations in stimulating innate immunity, offer opportunities to improve candidate vaccine designs intended to protect against HIV-1 acquisition. Recent findings Currently, major efforts in vaccine development focus on improving prime-boost vaccine regimens to enhance efficacy beyond 31% observed in the RV144 phase 3 study, and to develop a pathway to induce broadly reactive HIV neutralizing antibodies. Advances in HIV-1 Env immunogen design and improved adjuvant formulations are moving at a parallel pace. This review highlights steps underway to rationally pair vaccine concepts with improved adjuvant formulations in preclinical and early phase 1 clinical evaluation. Summary New adjuvants with immune potentiating properties are currently being tested in combination with recent HIV envelope-containing immunogens in prime-boost and subunit protein-only regimens. Greater emphasis is being applied to formulation science, delivery, and targeted safety and immune evaluation with these adjuvants in clinical trials. The need to develop an HIV vaccine that induces more potent and long-lived protective immunity will necessitate continued efforts to optimize adjuvanted vaccine formulations.

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“…Therefore, polymers that are able to induce a DAMP response similar to an adjuvant whilst delivering antiviral siRNAs may be beneficial in acute antiviral treatment [134,135]. This approach is currently being investigated for polymer-peptide-based vaccines and mRNA and pDNA vaccines against a range of viruses [136][137][138][139][140][141][142][143].…”

Section: Safety and Immune System Activation And Potential Adjuvant Ementioning

confidence: 99%

Polymers in the Delivery of siRNA for the Treatment of Virus Infections

2017

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Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a "magic bullet", due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence. Of particular interest was the potential for attenuating viral mRNAs contributing to the pathogenesis of disease that were not able to be targeted by vaccines or antiviral drugs. However, it was soon discovered that delivery of active siRNA molecules to the infection site in vivo was considerably more difficult than anticipated, due to a number of physiological barriers in the body. This spurred a new wave of investigation into nucleic acid delivery vehicles which could facilitate safe, targeted and effective administration of the siRNA as therapy. Amongst these, cationic polymer delivery vehicles have emerged as a promising candidate as they are low-cost and easy to produce at an industrial scale, and bind to the siRNA by non-specific electrostatic interactions. These nanoparticles (NPs) can be functionally designed to target the infection site, improve uptake in infected cells, release the siRNA inside the endosome and facilitate delivery into the cell cytoplasm. They may also have the added benefit of acting as adjuvants. This chapter provides a background around problems associated with the translation of siRNA as antiviral treatments, reviews the progress made in nucleic acid therapeutics and discusses current methods and progress in overcoming these challenges. It also addresses the importance of combining physicochemical characterisation of the NPs with in vitro and in vivo data.

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Thermoresponsive Polymer Nanoparticles Co-deliver RSV F Trimers with a TLR-7/8 Adjuvant

Cited by 46 publications

References 86 publications

Harnessing self-assembled peptide nanoparticles in epitope vaccine design

Harnessing self-assembled peptide nanoparticles in epitope vaccine design

Adjuvants

Polymers in the Delivery of siRNA for the Treatment of Virus Infections

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