Anti-RSV Peptide-Loaded Liposomes for the Inhibition of Respiratory Syncytial Virus

Joshi, Sameer; Chaudhari, Atul A.; Dennis, Vida A.; Kirby, Daniel; Perrie, Yvonne; Singh, Shree R.

doi:10.3390/bioengineering5020037

Cited by 15 publications

(9 citation statements)

References 46 publications

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“… 4 , 51 − 54 This approach can be extended to other nanostructures like lipid vesicles and droplets where there will be much greater control in incorporating specific oleosins distributed uniformly within the vesicle population. 26 , 55 , 56 …”

Section: Discussionmentioning

confidence: 99%

Recombinant Protein Micelles to Block Transduction by SARS-CoV-2 Pseudovirus

et al. 2022

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The continuing emergence of variants of the SARS-CoV-2 virus requires the development of modular molecular therapies. Here, we engineered a recombinant amphiphilic protein, oleosin, to spontaneously self-assemble into multivalent micellar nanostructures which can block the Spike S1 protein of SARS-CoV-2 pseudoviruses (PVs). Short recombinant proteins like oleosin can be formulated more easily than antibodies and can be functionalized with precision through genetic engineering. We cloned S1-binding mini-protein genes called LCB x, previously designed by David Baker’s laboratory (UW Seattle), to the N-terminus of oleosin, expressing Oleo-LCB x proteins in E. coli . These proteins largely formed 10–100 nm micelles as verified by dynamic light scattering. Two proteins, Oleo-LCB1 and Oleo-LCB3, were seen to completely and irreversibly block transduction by both wild-type and delta variant PVs into 293T-hsACE2 cells at 10 μM. Presented in multivalent micelles, these proteins reduced transduction by PVs down to a functional protein concentration of 5 nM. Additionally, Oleo-LCB1 micelles outperformed corresponding synthetic LCB1 mini-proteins in reducing transduction by PVs. Tunable aqueous solubility of recombinant oleosin allowed incorporation of peptides/mini-proteins at high concentrations within micelles, thus enhancing drug loading. To validate the potential multifunctionality of the micelles, we showed that certain combinations of Oleo-LCB1 and Oleo-LCB3 performed much better than the individual proteins at the same concentration. These micelles, which we showed to be non-toxic to human cells, are thus a promising step toward the design of modular, multifunctional therapeutics that could bind to and inactivate multiple receptors and proteins necessary for the infection of the SARS-CoV-2 virus.

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Section: Discussionmentioning

confidence: 99%

Recombinant Protein Micelles to Block Transduction by SARS-CoV-2 Pseudovirus

et al. 2022

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“…Surprisingly, the liposomes alone showed a higher level of RSV inhibition compared to the RF-482 peptide. This proves that empty liposomes themselves can serve as potential RSV inhibitors, whilst the anti-RSV peptide-loaded liposomes can significantly increase RSV inhibition when compared with the anti-RSV peptide alone [86]. Recently, a comprehensive review of liposomes specifically as a promising carrier for RSV was published [117].…”

Section: Liposomal Vaccines For Respiratory Syncytial Virus (Rsv)mentioning

confidence: 96%

Brief on Recent Application of Liposomal Vaccines for Lower Respiratory Tract Viral Infections: From Influenza to COVID-19 Vaccines

et al. 2021

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Vaccination is the most effective means of preventing infectious diseases and saving lives. Modern biotechnology largely enabled vaccine development. In the meantime, recent advances in pharmaceutical technology have resulted in the emergence of nanoparticles that are extensively investigated as promising miniaturized drug delivery systems. Scientists are particularly interested in liposomes as an important carrier for vaccine development. Wide acceptability of liposomes lies in their flexibility and versatility. Due to their unique vesicular structure with alternating aqueous and lipid compartments, liposomes can enclose both hydrophilic and lipophilic compounds, including antigens. Liposome composition can be tailored to obtain the desired immune response and adjuvant characteristics. During the current pandemic of COVID-19, many liposome-based vaccines have been developed with great success. This review covers a liposome-based vaccine designed particularly to combat viral infection of the lower respiratory tract (LRT), i.e., infection of the lung, specifically in the lower airways. Viruses such as influenza, respiratory syncytial virus (RSV), severe acute respiratory syndrome (SARS-CoV-1 and SARS-CoV-2) are common causes of LRT infections, hence this review mainly focuses on this category of viruses.

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“…Liposomes can be used as carriers for active therapeutic agents, such as antigens and immunomodulators, and thus liposomes show potential in vaccine adjuvant systems. Liposomes themselves can serve as potential inhibitors of respiratory syncytial virus (RSV), and compared to anti-RSV peptides alone, liposomes with anti-RSV peptides can significantly increase the inhibition of RSV [ 78 ]. Glucopyranosyl lipid adjuvant-stable emulsion is particularly effective in enhancing protection against H5N1 virus infection, inducing a continuous versatile (up to 6 months) and cross-reactive hemagglutinin-specific CD4 + T cell response at low doses [ 79 ].…”

Section: Nanoparticles As Vaccine Adjuvants In Antiviral Infectionmentioning

confidence: 99%

Design and application of nanoparticles as vaccine adjuvants against human corona virus infection

Mao

Chen

Wang

et al. 2021

Journal of Inorganic Biochemistry

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In recent years, some viruses have caused a grave crisis to global public health, especially the human coronavirus. A truly effective vaccine is therefore urgently needed. Vaccines should generally have two features: delivering antigens and modulating immunity. Adjuvants have an unshakable position in the battle against the virus. In addition to the perennial use of aluminium adjuvant, nanoparticles have become the developing adjuvant candidates due to their unique properties. Here we introduce several typical nanoparticles and their antivirus vaccine adjuvant applications. Finally, for the combating of the coronavirus, we propose several design points, hoping to provide ideas for the development of personalized vaccines and adjuvants and accelerate the clinical application of adjuvants.

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Anti-RSV Peptide-Loaded Liposomes for the Inhibition of Respiratory Syncytial Virus

Cited by 15 publications

References 46 publications

Recombinant Protein Micelles to Block Transduction by SARS-CoV-2 Pseudovirus

Recombinant Protein Micelles to Block Transduction by SARS-CoV-2 Pseudovirus

Brief on Recent Application of Liposomal Vaccines for Lower Respiratory Tract Viral Infections: From Influenza to COVID-19 Vaccines

Design and application of nanoparticles as vaccine adjuvants against human corona virus infection

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