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Article ; Online: Evolutionary dynamics of dengue virus in India.

Jagtap, Suraj / Pattabiraman, Chitra / Sankaradoss, Arun / Krishna, Sudhir / Roy, Rahul

2023 Volume 19, Issue 4, Page(s) e1010862

Abstract: More than a hundred thousand dengue cases are diagnosed in India annually, and about half of the country's population carries dengue virus-specific antibodies. Dengue propagates and adapts to the selection pressures imposed by a multitude of factors that ...

Abstract	More than a hundred thousand dengue cases are diagnosed in India annually, and about half of the country's population carries dengue virus-specific antibodies. Dengue propagates and adapts to the selection pressures imposed by a multitude of factors that can lead to the emergence of new variants. Yet, there has been no systematic analysis of the evolution of the dengue virus in the country. Here, we present a comprehensive analysis of all DENV gene sequences collected between 1956 and 2018 from India. We examine the spatio-temporal dynamics of India-specific genotypes, their evolutionary relationship with global and local dengue virus strains, interserotype dynamics and their divergence from the vaccine strains. Our analysis highlights the co-circulation of all DENV serotypes in India with cyclical outbreaks every 3-4 years. Since 2000, genotype III of DENV-1, cosmopolitan genotype of DENV-2, genotype III of DENV-3 and genotype I of DENV-4 have been dominating across the country. Substitution rates are comparable across the serotypes, suggesting a lack of serotype-specific evolutionary divergence. Yet, the envelope (E) protein displays strong signatures of evolution under immune selection. Apart from drifting away from its ancestors and other contemporary serotypes in general, we find evidence for recurring interserotype drift towards each other, suggesting selection via cross-reactive antibody-dependent enhancement. We identify the emergence of the highly divergent DENV-4-Id lineage in South India, which has acquired half of all E gene mutations in the antigenic sites. Moreover, the DENV-4-Id is drifting towards DENV-1 and DENV-3 clades, suggesting the role of cross-reactive antibodies in its evolution. Due to the regional restriction of the Indian genotypes and immunity-driven virus evolution in the country, ~50% of all E gene differences with the current vaccines are focused on the antigenic sites. Our study shows how the dengue virus evolution in India is being shaped in complex ways.
MeSH term(s)	Humans ; Dengue Virus/genetics ; Dengue/epidemiology ; Dengue/genetics ; Phylogeny ; Viral Envelope Proteins/genetics ; Serogroup ; Genotype ; India/epidemiology
Chemical Substances	Viral Envelope Proteins
Language	English
Publishing date	2023-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010862
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Evolutionary dynamics of dengue virus in India.

Suraj Jagtap / Chitra Pattabiraman / Arun Sankaradoss / Sudhir Krishna / Rahul Roy

PLoS Pathogens, Vol 19, Iss 4, p e

2023 Volume 1010862

Abstract	More than a hundred thousand dengue cases are diagnosed in India annually, and about half of the country's population carries dengue virus-specific antibodies. Dengue propagates and adapts to the selection pressures imposed by a multitude of factors that can lead to the emergence of new variants. Yet, there has been no systematic analysis of the evolution of the dengue virus in the country. Here, we present a comprehensive analysis of all DENV gene sequences collected between 1956 and 2018 from India. We examine the spatio-temporal dynamics of India-specific genotypes, their evolutionary relationship with global and local dengue virus strains, interserotype dynamics and their divergence from the vaccine strains. Our analysis highlights the co-circulation of all DENV serotypes in India with cyclical outbreaks every 3-4 years. Since 2000, genotype III of DENV-1, cosmopolitan genotype of DENV-2, genotype III of DENV-3 and genotype I of DENV-4 have been dominating across the country. Substitution rates are comparable across the serotypes, suggesting a lack of serotype-specific evolutionary divergence. Yet, the envelope (E) protein displays strong signatures of evolution under immune selection. Apart from drifting away from its ancestors and other contemporary serotypes in general, we find evidence for recurring interserotype drift towards each other, suggesting selection via cross-reactive antibody-dependent enhancement. We identify the emergence of the highly divergent DENV-4-Id lineage in South India, which has acquired half of all E gene mutations in the antigenic sites. Moreover, the DENV-4-Id is drifting towards DENV-1 and DENV-3 clades, suggesting the role of cross-reactive antibodies in its evolution. Due to the regional restriction of the Indian genotypes and immunity-driven virus evolution in the country, ~50% of all E gene differences with the current vaccines are focused on the antigenic sites. Our study shows how the dengue virus evolution in India is being shaped in complex ways.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Construction, analysis and validation of co-expression network to understand stress adaptation in Deinococcus radiodurans R1.

Joshi, Suraj R / Jagtap, Surabhi / Basu, Bhakti / Deobagkar, Deepti D / Ghosh, Payel

PloS one

2020 Volume 15, Issue 6, Page(s) e0234721

Abstract: Systems biology based approaches have been effectively utilized to mine high throughput data. In the current study, we have performed system-level analysis for Deinococcus radiodurans R1 by constructing a gene co-expression network based on several ... ...

Abstract	Systems biology based approaches have been effectively utilized to mine high throughput data. In the current study, we have performed system-level analysis for Deinococcus radiodurans R1 by constructing a gene co-expression network based on several microarray datasets available in the public domain. This condition-independent network was constructed by Weighted Gene Co-expression Network Analysis (WGCNA) with 61 microarray samples from 9 different experimental conditions. We identified 13 co-expressed modules, of which, 11 showed functional enrichments of one or more pathway/s or biological process. Comparative analysis of differentially expressed genes and proteins from radiation and desiccation stress studies with our co-expressed modules revealed the association of cyan with radiation response. Interestingly, two modules viz darkgreen and tan was associated with radiation as well as desiccation stress responses. The functional analysis of these modules showed enrichment of pathways important for adaptation of radiation or desiccation stress. To decipher the regulatory roles of these stress responsive modules, we identified transcription factors (TFs) and then calculated a Biweight mid correlation between modules hub gene and the identified TFs. We obtained 7 TFs for radiation and desiccation responsive modules. The expressions of 3 TFs were validated in response to gamma radiation using qRT-PCR. Along with the TFs, selected close neighbor genes of two important TFs, viz., DR_0997 (CRP) and DR_2287 (AsnC family transcriptional regulator) in the darkgreen module were also validated. In our network, among 13 hub genes associated with 13 modules, the functionality of 5 hub genes which are annotated as hypothetical proteins (hypothetical hub genes) in D. radiodurans genome has been revealed. Overall the study provided a better insight of pathways and regulators associated with relevant DNA damaging stress response in D. radiodurans.
MeSH term(s)	Adaptation, Physiological/genetics ; Deinococcus/genetics ; Deinococcus/physiology ; Gene Regulatory Networks ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; Stress, Physiological ; Systems Biology
Language	English
Publishing date	2020-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0234721
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Article ; Online: Construction, analysis and validation of co-expression network to understand stress adaptation in Deinococcus radiodurans R1.

Suraj R Joshi / Surabhi Jagtap / Bhakti Basu / Deepti D Deobagkar / Payel Ghosh

PLoS ONE, Vol 15, Iss 6, p e

2020 Volume 0234721

Abstract	Systems biology based approaches have been effectively utilized to mine high throughput data. In the current study, we have performed system-level analysis for Deinococcus radiodurans R1 by constructing a gene co-expression network based on several microarray datasets available in the public domain. This condition-independent network was constructed by Weighted Gene Co-expression Network Analysis (WGCNA) with 61 microarray samples from 9 different experimental conditions. We identified 13 co-expressed modules, of which, 11 showed functional enrichments of one or more pathway/s or biological process. Comparative analysis of differentially expressed genes and proteins from radiation and desiccation stress studies with our co-expressed modules revealed the association of cyan with radiation response. Interestingly, two modules viz darkgreen and tan was associated with radiation as well as desiccation stress responses. The functional analysis of these modules showed enrichment of pathways important for adaptation of radiation or desiccation stress. To decipher the regulatory roles of these stress responsive modules, we identified transcription factors (TFs) and then calculated a Biweight mid correlation between modules hub gene and the identified TFs. We obtained 7 TFs for radiation and desiccation responsive modules. The expressions of 3 TFs were validated in response to gamma radiation using qRT-PCR. Along with the TFs, selected close neighbor genes of two important TFs, viz., DR_0997 (CRP) and DR_2287 (AsnC family transcriptional regulator) in the darkgreen module were also validated. In our network, among 13 hub genes associated with 13 modules, the functionality of 5 hub genes which are annotated as hypothetical proteins (hypothetical hub genes) in D. radiodurans genome has been revealed. Overall the study provided a better insight of pathways and regulators associated with relevant DNA damaging stress response in D. radiodurans.
Keywords	Medicine ; R ; Science ; Q
Subject code	572 ; 570
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Purification, biochemical characterization and structural modelling of alkali-stable β-1,4-xylan xylanohydrolase from Aspergillus fumigatus R1 isolated from soil.

Deshmukh, Rehan Ahmed / Jagtap, Sharmili / Mandal, Madan Kumar / Mandal, Suraj Kumar

BMC biotechnology

2016 Volume 16, Page(s) 11

Abstract: Background: Aspergillus fumigatus R1 produced xylanase under submerged fermentation which degrades the complex hemicelluloses contained in agricultural substrates. Xylanases have gained considerable attention because of their tremendous applications in ... ...

Abstract	Background: Aspergillus fumigatus R1 produced xylanase under submerged fermentation which degrades the complex hemicelluloses contained in agricultural substrates. Xylanases have gained considerable attention because of their tremendous applications in industries. The purpose of our study was to purify xylanase and study its biochemical properties. We have predicted the secondary structure of purified xylanase and evaluated its active site residues and substrate binding sites based on the global and local structural similarity. Results: Various microorganisms were isolated from Puducherry soil and screened by Congo-red test. The best isolate was identified to be Aspergillus fumigatus R1. The production kinetics showed the highest xylanase production (208 IU/ml) by this organism in 96 h using 1 % rice bran as the only carbon source. The purification of extracellular xylanase was carried out by fractional ammonium sulphate precipitation (30-55 %), followed by extensive dialysis and Bio-Gel P-60 Gel-filtration chromatography. The enzyme was purified 58.10 folds with a specific activity of 38196.22 IU/mg. The biochemical characterization of the pure enzyme was carried out for its optimum pH and temperature (5.0 and 50(0)C), pH and temperature stability, molecular mass (Mr) (24.5 kDa) and pI (6.29). The complete sequence of protein was obtained by mass spectrometry analysis. Apparent Km and Vmax values of the xylanase for birchwood xylan were 11.66 mg/ml and 87.6 μmol min(-1) mg(-1) respectively. Conclusion: Purified xylanase was analyzed by mass-spectrometry which revealed 2 unique peptides. Xylanase under current study showed significant production using agricultural residues and a broad range of pH stability in the alkaline region. Xylanase produced by Aspergillus fumigatus R1 could serve as the enzyme of choice in industries.
MeSH term(s)	Amino Acid Sequence ; Aspergillus fumigatus/enzymology ; Aspergillus fumigatus/genetics ; Endo-1,4-beta Xylanases/chemistry ; Endo-1,4-beta Xylanases/genetics ; Endo-1,4-beta Xylanases/isolation & purification ; Endo-1,4-beta Xylanases/metabolism ; Enzyme Stability ; Hydrogen-Ion Concentration ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Soil Microbiology ; Temperature
Chemical Substances	Endo-1,4-beta Xylanases (EC 3.2.1.8)
Language	English
Publishing date	2016-02-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1472-6750
ISSN (online)	1472-6750
DOI	10.1186/s12896-016-0242-4
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Article ; Online: Evaluation of spike protein antigens for SARS-CoV-2 serology.

Jagtap, Suraj / K, Ratnasri / Valloly, Priyanka / Sharma, Rakhi / Maurya, Satyaghosh / Gaigore, Anushree / Ardhya, Chitra / Biligi, Dayananda S / Desiraju, Bapu Koundinya / Natchu, Uma Chandra Mouli / Saini, Deepak Kumar / Roy, Rahul

Journal of virological methods

2021 Volume 296, Page(s) 114222

Abstract: Background: Spike protein domains are being used in various serology-based assays to detect prior exposure to SARS-CoV-2 virus. However, there has been limited comparison of antibody titers against various spike protein antigens among COVID-19 infected ... ...

Abstract	Background: Spike protein domains are being used in various serology-based assays to detect prior exposure to SARS-CoV-2 virus. However, there has been limited comparison of antibody titers against various spike protein antigens among COVID-19 infected patients. Methods: We compared four spike proteins (RBD, S1, S2 and a stabilized spike trimer (ST)) representing commonly used antigens for their reactivity to human IgG antibodies using indirect ELISA in serum from COVID-19 patients and pre-2020 samples. ST ELISA was also compared against the EUROIMMUN IgG ELISA test. Further, we estimated time appropriate IgG and IgA seropositivity rates in COVID-19 patients using a panel of sera samples collected longitudinally from the day of onset of symptoms (DOS). Results: Among the four spike antigens tested, the ST demonstrated the highest sensitivity (86.2 %; 95 % CI: 77.8-91.7 %), while all four antigens showed high specificity to COVID-19 sera (94.7-96.8 %). 13.8 % (13/94) of the samples did not show seroconversion in any of the four antigen-based assays. In a double-blinded head-to-head comparison, ST based IgG ELISA displayed a better sensitivity (87.5 %, 95 % CI: 76.4-93.8 %) than the EUROIMMUN IgG ELISA (67.9 %, 95 % CI: 54.8-78.6 %). Further, in ST-based assays, we found 48 % and 50 % seroconversion in the first six days (from DOS) for IgG and IgA antibodies, respectively, which increased to 84 % (IgG) and 85 % (IgA) for samples collected ≥22 days from DOS. Conclusions: Comparison of spike antigens demonstrates that spike trimer protein is a superior option as an ELISA antigen for COVID-19 serology.
MeSH term(s)	Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antigens, Viral/blood ; Antigens, Viral/immunology ; COVID-19/blood ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19 Serological Testing/methods ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Immunoglobulin A/blood ; Immunoglobulin A/immunology ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; SARS-CoV-2/immunology ; Sensitivity and Specificity ; Seroconversion ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	Antibodies, Viral ; Antigens, Viral ; Immunoglobulin A ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-06-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2021.114222
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Article: Evaluation of spike protein antigens for SARS-CoV-2 serology

Jagtap, Suraj / K, Ratnasri / Valloly, Priyanka / Sharma, Rakhi / Maurya, Satyaghosh / Gaigore, Anushree / Ardhya, Chitra / Biligi, Dayananda S. / Desiraju, Bapu Koundinya / Natchu, Uma Chandra Mouli / Saini, Deepak Kumar / Roy, Rahul

Journal of virological methods. 2021 Oct., v. 296

2021

Abstract: Spike protein domains are being used in various serology-based assays to detect prior exposure to SARS-CoV-2 virus. However, there has been limited comparison of antibody titers against various spike protein antigens among COVID-19 infected patients.We ... ...

Abstract	Spike protein domains are being used in various serology-based assays to detect prior exposure to SARS-CoV-2 virus. However, there has been limited comparison of antibody titers against various spike protein antigens among COVID-19 infected patients.We compared four spike proteins (RBD, S1, S2 and a stabilized spike trimer (ST)) representing commonly used antigens for their reactivity to human IgG antibodies using indirect ELISA in serum from COVID-19 patients and pre-2020 samples. ST ELISA was also compared against the EUROIMMUN IgG ELISA test. Further, we estimated time appropriate IgG and IgA seropositivity rates in COVID-19 patients using a panel of sera samples collected longitudinally from the day of onset of symptoms (DOS).Among the four spike antigens tested, the ST demonstrated the highest sensitivity (86.2 %; 95 % CI: 77.8–91.7 %), while all four antigens showed high specificity to COVID-19 sera (94.7–96.8 %). 13.8 % (13/94) of the samples did not show seroconversion in any of the four antigen-based assays. In a double-blinded head-to-head comparison, ST based IgG ELISA displayed a better sensitivity (87.5 %, 95 % CI: 76.4–93.8 %) than the EUROIMMUN IgG ELISA (67.9 %, 95 % CI: 54.8–78.6 %). Further, in ST-based assays, we found 48 % and 50 % seroconversion in the first six days (from DOS) for IgG and IgA antibodies, respectively, which increased to 84 % (IgG) and 85 % (IgA) for samples collected ≥22 days from DOS.Comparison of spike antigens demonstrates that spike trimer protein is a superior option as an ELISA antigen for COVID-19 serology.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antibodies ; antigens ; blood serum ; humans ; seroconversion ; serology ; seroprevalence ; viruses
Language	English
Dates of publication	2021-10
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2021.114222
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Evaluation of spike protein antigens for SARS-CoV-2 serology

Jagtap, Suraj / K, Ratnasri / Valloly, Priyanka / Sharma, Rakhi / Maurya, Satyaghosh / Gaigore, Anushree / Ardhya, Chitra / Biligi, Dayanand S. / Desiraju, Bapu Koundinya / Natchu, Uma Chandra Mouli / Saini, Deepak Kumar / Roy, Rahul

medRxiv

Abstract: Background: Spike protein domains are being used in various serology-based assays to detect prior exposure to SARS-CoV-2 virus. However, there has been limited comparison of human antibody titers against various spike protein antigens among COVID-19 ... ...

Abstract	Background: Spike protein domains are being used in various serology-based assays to detect prior exposure to SARS-CoV-2 virus. However, there has been limited comparison of human antibody titers against various spike protein antigens among COVID-19 infected patients. Methods: We compared four spike proteins (RBD, S1, S2 and a stabilized spike trimer (ST)) representing commonly used antigens for their reactivity to human IgG antibodies using indirect ELISA in serum from COVID-19 patients and pre-2020 samples. ST ELISA was also compared against the EUROIMMUN IgG ELISA test. Further, we estimated time appropriate IgG and IgA seropositivity rates in COVID-19 patients using a panel of sera samples collected longitudinally from the day of onset of symptoms (DOS). Results: Among the four spike antigens tested, the ST demonstrated the highest sensitivity (86.2%; 95% CI: 77.8-91.7%), while all four antigens showed high specificity to COVID-19 sera (94.7-96.8%). 13.8% (13/94) of the samples did not show seroconversion in any of the four antigen-based assays. In a double-blinded head-to-head comparison, ST based IgG ELISA displayed a better sensitivity (87.5%, 95%CI: 76.4-93.8%) than the EUROIMMUN IgG ELISA (67.9%, 95% CI: 54.8-78.6%). Further, in ST-based assays, we found 48% and 50% seroconversion in the first six days (from DOS) for IgG and IgA antibodies, respectively, which increased to 84% (IgG) and 85% (IgA) for samples collected ≥22 days DOS. Conclusions: Comparison of spike antigens demonstrates that spike trimer protein is a superior option as an ELISA antigen for COVID-19 serology.
Keywords	covid19
Language	English
Publishing date	2021-01-29
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.01.27.21250382
Database	COVID19

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Article: Purification, biochemical characterization and structural modelling of alkali-stable β-1,4-xylan xylanohydrolase from Aspergillus fumigatus R1 isolated from soil

Deshmukh, Rehan Ahmed / Madan Kumar Mandal / Sharmili Jagtap / Suraj Kumar Mandal

BMC biotechnology. 2016 Dec., v. 16, no. 1

2016

Abstract: BACKGROUND: Aspergillus fumigatus R1 produced xylanase under submerged fermentation which degrades the complex hemicelluloses contained in agricultural substrates. Xylanases have gained considerable attention because of their tremendous applications in ... ...

Abstract	BACKGROUND: Aspergillus fumigatus R1 produced xylanase under submerged fermentation which degrades the complex hemicelluloses contained in agricultural substrates. Xylanases have gained considerable attention because of their tremendous applications in industries. The purpose of our study was to purify xylanase and study its biochemical properties. We have predicted the secondary structure of purified xylanase and evaluated its active site residues and substrate binding sites based on the global and local structural similarity. RESULTS: Various microorganisms were isolated from Puducherry soil and screened by Congo-red test. The best isolate was identified to be Aspergillus fumigatus R1. The production kinetics showed the highest xylanase production (208 IU/ml) by this organism in 96 h using 1 % rice bran as the only carbon source. The purification of extracellular xylanase was carried out by fractional ammonium sulphate precipitation (30–55 %), followed by extensive dialysis and Bio-Gel P-60 Gel-filtration chromatography. The enzyme was purified 58.10 folds with a specific activity of 38196.22 IU/mg. The biochemical characterization of the pure enzyme was carried out for its optimum pH and temperature (5.0 and 500C), pH and temperature stability, molecular mass (Mr) (24.5 kDa) and pI (6.29). The complete sequence of protein was obtained by mass spectrometry analysis. Apparent Km and Vmax values of the xylanase for birchwood xylan were 11.66 mg/ml and 87.6 μmol min−1 mg−1 respectively. CONCLUSION: Purified xylanase was analyzed by mass-spectrometry which revealed 2 unique peptides. Xylanase under current study showed significant production using agricultural residues and a broad range of pH stability in the alkaline region. Xylanase produced by Aspergillus fumigatus R1 could serve as the enzyme of choice in industries.
Keywords	active sites ; agricultural wastes ; ammonium sulfate ; Aspergillus fumigatus ; binding sites ; carbon ; dialysis ; gel chromatography ; industry ; mass spectrometry ; microorganisms ; models ; molecular weight ; peptides ; pH ; rice bran ; soil ; submerged fermentation ; temperature ; xylan ; xylanases
Language	English
Dates of publication	2016-12
Size	p. 11.
Publishing place	BioMed Central
Document type	Article
ISSN	1472-6750
DOI	10.1186/s12896-016-0242-4
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences.

Sankaradoss, Arun / Jagtap, Suraj / Nazir, Junaid / Moula, Shefta E / Modak, Ayan / Fialho, Joshuah / Iyer, Meenakshi / Shastri, Jayanthi S / Dias, Mary / Gadepalli, Ravisekhar / Aggarwal, Alisha / Vedpathak, Manoj / Agrawal, Sachee / Pandit, Awadhesh / Nisheetha, Amul / Kumar, Anuj / Bordoloi, Mahasweta / Shafi, Mohamed / Shelar, Bhagyashree /

Balachandra, Swathi S / Damodar, Tina / Masika, Moses Muia / Mwaura, Patrick / Anzala, Omu / Muthumani, Kar / Sowdhamini, Ramanathan / Medigeshi, Guruprasad R / Roy, Rahul / Pattabiraman, Chitra / Krishna, Sudhir / Sreekumar, Easwaran

Molecular therapy : the journal of the American Society of Gene Therapy

2022 Volume 30, Issue 5, Page(s) 2058–2077

Abstract: The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining ...

Abstract	The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1-4 and a dengue virus (DENV)-2 non-structural protein 1 (NS1) protein-coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on the whole genome sequencing of clinical isolates in India and complemented with data from Africa. This sequence was further optimized for protein expression. In silico structural analysis of the EDIII consensus sequence revealed that epitopes are structurally conserved and immunogenic. The vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying intracellular interferon (IFN)-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios, and immune gene profiling suggests a strong Th1-dominant immune response. Finally, the passive transfer of immune sera protected AG129 mice challenged with a virulent, non-mouse-adapted DENV-2 strain. Our findings collectively suggest an alternative strategy for dengue vaccine design by offering a novel vaccine candidate with a possible broad-spectrum protection and a successful clinical translation either as a stand alone or in a mix and match strategy.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Dengue/prevention & control ; Dengue Vaccines/genetics ; Dengue Virus/genetics ; Humans ; Pandemics ; Vaccines, DNA ; Viral Envelope Proteins/genetics
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Dengue Vaccines ; Vaccines, DNA ; Viral Envelope Proteins
Language	English
Publishing date	2022-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2022.01.013
Database	MEDical Literature Analysis and Retrieval System OnLINE

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