Protein Crystallography in Vaccine Research and Development

Malito, E.; Carfı́, Andrea; Bottomley, Matthew J.

doi:10.3390/ijms160613106

Cited by 52 publications

(30 citation statements)

References 179 publications

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“…B cell epitope (variable region of protective antibodies in contact with infectious antigens) mapping is important for the development of effective vaccines in support of sero-diagnostics. This technique identifies protective epitopes for vaccine development and the estimation of conventional vaccines (killed or attenuated pathogens; Malito et al, 2015).…”

Section: Immuno-protective Epitope Mappingmentioning

confidence: 99%

Antibody Engineering for Pursuing a Healthier Future

et al. 2017

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Since the development of antibody-production techniques, a number of immunoglobulins have been developed on a large scale using conventional methods. Hybridoma technology opened a new horizon in the production of antibodies against target antigens of infectious pathogens, malignant diseases including autoimmune disorders, and numerous potent toxins. However, these clinical humanized or chimeric murine antibodies have several limitations and complexities. Therefore, to overcome these difficulties, recent advances in genetic engineering techniques and phage display technique have allowed the production of highly specific recombinant antibodies. These engineered antibodies have been constructed in the hunt for novel therapeutic drugs equipped with enhanced immunoprotective abilities, such as engaging immune effector functions, effective development of fusion proteins, efficient tumor and tissue penetration, and high-affinity antibodies directed against conserved targets. Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines. However, there is limited knowledge regarding dynamic antibody development approaches. Therefore, this review extends beyond our understanding of conventional polyclonal and monoclonal antibodies. Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans.

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Section: Immuno-protective Epitope Mappingmentioning

confidence: 99%

Antibody Engineering for Pursuing a Healthier Future

et al. 2017

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“…Encouraged by recent results from HIV‐1 VLPs (C. Zhao, Ao, & Yao, ), structural biology is emerging as a powerful tool to assist in the rational design of a modern HIV VLP vaccine. Novel protective epitopes can now be identified in conformational epitope mapping studies via structural biology (Liljeroos et al, ; Malito, Carfi, & Bottomley, ). In addition, broad and potent HIV antibodies discovered in the pool of antigen‐specific memory B cells using structural biology, highlight novel sites of vulnerability on HIV envelope glycoprotein epitope (J. Huang et al, ).…”

Section: Design Tools For Modern Vaccinesmentioning

confidence: 99%

Synthetic biology for bioengineering virus‐like particle vaccines

Hume

Vidigal

Carrondo

et al. 2018

Biotech & Bioengineering

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Vaccination is the most effective method of disease prevention and control. Many viruses and bacteria that once caused catastrophic pandemics (e.g., smallpox, poliomyelitis, measles, and diphtheria) are either eradicated or effectively controlled through routine vaccination programs. Nonetheless, vaccine manufacturing remains incredibly challenging. Viruses exhibiting high antigenic diversity and high mutation rates cannot be fairly contested using traditional vaccine production methods and complexities surrounding the manufacturing processes, which impose significant limitations. Virus-like particles (VLPs) are recombinantly produced viral structures that exhibit immunoprotective traits of native viruses but are noninfectious. SeveralVLPs that compositionally match a given natural virus have been developed and licensed as vaccines. Expansively, a plethora of studies now confirms that VLPs can be designed to safely present heterologous antigens from a variety of pathogens unrelated to the chosen carrier VLPs. Owing to this design versatility, VLPs offer technological opportunities to modernize vaccine supply and disease response through rational bioengineering. These opportunities are greatly enhanced with the application of synthetic biology, the redesign and construction of novel biological entities. This review outlines how synthetic biology is currently applied to engineer VLP functions and manufacturing process. Current and developing technologies for the identification of novel target-specific antigens and their usefulness for rational engineering of VLP functions (e.g., presentation of structurally diverse antigens, enhanced antigen immunogenicity, and improved vaccine stability) are described.When applied to manufacturing processes, synthetic biology approaches can also overcome specific challenges in VLP vaccine production. Finally, we address several challenges and benefits associated with the translation of VLP vaccine development into the industry. K E Y W O R D S

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“…Among the structural techniques, X‐ray diffraction studies of an antigen–antibody complex can simultaneously provide the structure of the antigen of interest and unambiguously define the binding interface at atomic resolution . It is undoubtedly the method of choice to determine the antigen–antibody binding site but it requires high‐quality crystals of the complex, which may not always be successful.…”

Section: Structural Vaccinologymentioning

confidence: 99%

Structural Knowledge for Molecular Optimization: The Cases of Metal‐Mediated Protein–Protein Interactions and Structural Vaccinology

Cantini

Banci

2018

Eur J Inorg Chem

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The knowledge of the structural properties of molecules and of their recognition and interaction patterns with partners is a key feature for understanding their functional properties. This is particularly true for the comprehension of complex cellular processes in which several interacting proteins are involved. The structural characterization of all the molecules involved in a process allows the understanding of the malfunctioning of such process and eventually the design of biomole-[a] Magnetic Lucia Banci is a Professor of Chemistry at the University of Florence. She has extensive expertise and has provided original contributions and breakthroughs in Structural Biology and in biological NMR spectroscopy. She has addressed and unraveled many aspects of the biology of metal ions in biological systems. The innovative in cell NMR approach developed by Lucia Banci and her group allows for the detection of human individual proteins in living human cells with atomic level resolution. She also exploited the extensive knowledge of structural biology approaches through NMR expertise to develop an absolutely innovative approach to vaccine design, based on the knowledge of the structure of the pathogen antigens and of the interaction patterns with antibodies, to design structure-based vaccines. Francesca Cantini graduated in Chemistry in 2000 and received her PhD in Structural Biology in 2004 at the University of Florence. She is now a permanent research scientist at the University of Florence. Her research is focused on the structural and dynamic characterization of proteins and protein complexes through NMR spectroscopy. Since 2000, her research activity is dedicated to the comprehension of the molecular mechanisms responsible for metal trafficking and metallo-protein maturation. Since 2005, she collaborates with GSK Vaccines (Siena, Italy) on the structural characterization of vaccine candidates and their interaction with antibodies. Eur. J. Inorg. Chem. 2018, 4108-4116 4109mining protein recognition and interaction. Knowledge of such factors permits the description of cellular processes in a systemwide frame, as well as the understanding of the malfunctioning of such processes and the design of biomolecules to counterbalance it.

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Protein Crystallography in Vaccine Research and Development

Cited by 52 publications

References 179 publications

Antibody Engineering for Pursuing a Healthier Future

Antibody Engineering for Pursuing a Healthier Future

Synthetic biology for bioengineering virus‐like particle vaccines

Structural Knowledge for Molecular Optimization: The Cases of Metal‐Mediated Protein–Protein Interactions and Structural Vaccinology

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