A Bioinformatics approach to designing a Zika virus vaccine

Dey, Sumanta; Nandy, Ashesh; Basak, Subhash C.; Nandy, Papiya; Das, Sukhen

doi:10.1016/j.compbiolchem.2017.03.002

Cited by 28 publications

(30 citation statements)

References 29 publications

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“…A variety of methods, including mass spectrometry (MS)‐based approaches, have been developed for the identification of antibody‐specific epitopes and for providing structural information about antigen–antibody complexes. These methods also include X‐ray crystallography and NMR spectroscopy, immunoanalytical characterization of antigen–antibody interactions, and the design and synthesis of peptide–epitope mimotopes . Proteolytic excision–extraction mass spectrometry (PROTEX‐MS), hydrogen–deuterium exchange mass spectrometry (HDX‐MS) of peptide backbone hydrogen atoms, and fast‐photochemical oxidation of proteins are the major techniques for MS‐based elucidation of antibody epitopes, but these tools alone do not provide quantitative affinity data .…”

Section: Introductionmentioning

confidence: 99%

Antibody Epitope of Human α‐Galactosidase A Revealed by Affinity Mass Spectrometry: A Basis for Reversing Immunoreactivity in Enzyme Replacement Therapy of Fabry Disease

et al. 2018

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α-Galactosidase (αGal) is a lysosomal enzyme that hydrolyses the terminal α-galactosyl moiety from glycosphingolipids. Mutations in the encoding genes for αGal lead to defective or misfolded enzyme, which results in substrate accumulation and subsequent organ dysfunction. The metabolic disease caused by a deficiency of human α-galactosidase A is known as Fabry disease or Fabry-Anderson disease, and it belongs to a larger group known as lysosomal storage diseases. An effective treatment for Fabry disease has been developed by enzyme replacement therapy (ERT), which involves infusions of purified recombinant enzyme in order to increase enzyme levels and decrease the amounts of accumulated substrate. However, immunoreactivity and IgG antibody formation are major, therapy-limiting, and eventually life-threatening complications of ERT. The present study focused on the epitope determination of human α-galactosidase A against its antibody formed. Here we report the identification of the epitope of human αGal(309-332) recognized by a human monoclonal anti-αGal antibody, using a combination of proteolytic excision of the immobilized immune complex and surface plasmon resonance biosensing mass spectrometry. The epitope peptide, αGal(309-332), was synthesized by solid-phase peptide synthesis. Determination of its affinity by surface plasmon resonance analysis revealed a high binding affinity for the antibody (K =39×10 m), which is nearly identical to that of the full-length enzyme (K =16×10 m). The proteolytic excision affinity mass spectrometry method is shown here to be an efficient tool for epitope identification of an immunogenic lysosomal enzyme. Because the full-length αGal and the antibody epitope showed similar binding affinities, this provides a basis for reversing immunogenicity upon ERT by: 1) treatment of patients with the epitope peptide to neutralize antibodies, or 2) removal of antibodies by apheresis, and thus significantly improving the response to ERT.

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Section: Introductionmentioning

confidence: 99%

Antibody Epitope of Human α‐Galactosidase A Revealed by Affinity Mass Spectrometry: A Basis for Reversing Immunoreactivity in Enzyme Replacement Therapy of Fabry Disease

et al. 2018

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“…Applications of these methods to viral sequence analyses have been a prime area of interest in view of the need for rapid development of drugs and vaccines against viral diseases. In a number of studies, our group has advocated rational designs of peptide vaccines against Influenza [5], Rotavirus [6], Human Papillomavirus [7] and Zika virus [8]. In particular, we have worked out detailed differences between base distributions within the species of the Flavivirus genus and have shown that the Dengue virus which rapidly becomes endemic in a country or region has country/region-specific sequence differences, requiring customized vaccines for better efficacy [9].…”

Section: Introductionmentioning

confidence: 99%

Graphical representation methods: How well do they discriminate between homologous gene sequences?

et al. 2018

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“…Application to several human papillomavirus envelope protein [16] showed that there could be peptide vaccines that can inhibit several papillomaviral types at a time. In a more recent example, the technique has been applied to comparatively sparse data of the Zika virus [17] that have caused severe disruptions in the Americas in 2015-16.…”

Section: Mol2net 2017mentioning

confidence: 99%

<strong>A brief account of the search for peptide vaccines </strong>

Basak

Nandy

2017

Proceedings of MOL2NET 2017, International Conference on Multidisciplinary Sciences, 3rd Edition

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An increasing trend of viral diseases have led to search for faster response systems for preventives and therapeutics. While traditional vaccinations have led to spectacular successes against smallpox and polio viruses, the need for rapid response to new viral epidemics, like in the case of Ebola and Zika viruses, has called for new ways of tackling such infections. The fact that viral diseases are notoriously difficult to control, due primarily to their nature of fast mutational changes leading to growth of new strains and development of strains resistant to prevailing medications, adds an extra layer of complexity to the task. Peptide vaccines provide one means of responding to the epidemics. Since they are developed based on the viral sequences and focused on the antigenic sites, peptide vaccines are amenable to rational design paradigms. The first such vaccine for the canine parvovirus was developed in the 1990s and many peptide vaccines against human viral diseases are under different stages of phase trials. While production of such vaccines can be fast and cost-effective, and there are several issues still to be resolved, peptide vaccines are expected to play a major role in the future. In this very bried review we recount current status and some of the different approaches to design of peptide vaccines.

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A Bioinformatics approach to designing a Zika virus vaccine

Cited by 28 publications

References 29 publications

Antibody Epitope of Human α‐Galactosidase A Revealed by Affinity Mass Spectrometry: A Basis for Reversing Immunoreactivity in Enzyme Replacement Therapy of Fabry Disease

Antibody Epitope of Human α‐Galactosidase A Revealed by Affinity Mass Spectrometry: A Basis for Reversing Immunoreactivity in Enzyme Replacement Therapy of Fabry Disease

Graphical representation methods: How well do they discriminate between homologous gene sequences?

<strong>A brief account of the search for peptide vaccines </strong>

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