PCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection
العنوان: | PCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection |
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المؤلفون: | Corinne Cayatte, Angie Snell Bennett, Kirsten Schneider-Ohrum, Alexander K. Andrianov, Jason D. Marshall, Gaurav Manohar Rajani, Alexander Marin |
المصدر: | Molecular Pharmaceutics. 14:2285-2293 |
بيانات النشر: | American Chemical Society (ACS), 2017. |
سنة النشر: | 2017 |
مصطلحات موضوعية: | 0301 basic medicine, Antigenicity, Polymers, viruses, medicine.medical_treatment, Pharmaceutical Science, Enzyme-Linked Immunosorbent Assay, CHO Cells, 02 engineering and technology, Biology, medicine.disease_cause, Immunoadjuvant, Neutralization, Virus, Microbiology, Mice, 03 medical and health sciences, Cricetulus, Organophosphorus Compounds, Immunity, Drug Discovery, medicine, Animals, Humans, Immunity, Cellular, Mice, Inbred BALB C, Circular Dichroism, Immunogenicity, Viral Vaccines, respiratory system, 021001 nanoscience & nanotechnology, Antibodies, Neutralizing, Virology, Respiratory Syncytial Viruses, 030104 developmental biology, Respiratory syncytial virus (RSV), Immunoglobulin G, Molecular Medicine, 0210 nano-technology, Adjuvant |
الوصف: | PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV comparable to alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and in the upper respiratory tract. PCPP formulations were also characterized by Th1-biased responses, compared to Th2-biased responses that are more typical for RSV sF alone or RSV sF-alum formulations, suggesting an inherent immunostimulating activity of the polyphosphazene adjuvant. We defined these immunologically active RSV sF-PCPP formulations as self-assembled water-soluble protein-polymer complexes with distinct physicochemical parameters. The secondary structure and antigenicity of the protein in the complex were fully preserved during the spontaneous aqueous self-assembly process. These findings further advance the concept of polyphosphazene immunoadjuvants as unique dual-functionality adjuvants integrating delivery and immunostimulating modalities in one water-soluble molecule. |
تدمد: | 1543-8392 1543-8384 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc8989e09368a0de6005bd238f953697 https://doi.org/10.1021/acs.molpharmaceut.7b00118 |
رقم الأكسشن: | edsair.doi.dedup.....cc8989e09368a0de6005bd238f953697 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15438392 15438384 |
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