Huang C.Y.-H.,Centers for Disease Control and Prevention |
Kinney R.M.,Centers for Disease Control and Prevention |
Livengood J.A.,Inviragen |
Bolling B.,Centers for Disease Control and Prevention |
And 9 more authors.
PLoS Neglected Tropical Diseases
Background:We have developed a manufacturing strategy that can improve the safety and genetic stability of recombinant live-attenuated chimeric dengue vaccine (DENVax) viruses. These viruses, containing the pre-membrane (prM) and envelope (E) genes of dengue serotypes 1-4 in the replicative background of the attenuated dengue-2 PDK-53 vaccine virus candidate, were manufactured under cGMP.Methodology/Principal Findings:After deriving vaccine viruses from RNA-transfected Vero cells, six plaque-purified viruses for each serotype were produced. The plaque-purified strains were then analyzed to select one stock for generation of the master seed. Full genetic and phenotypic characterizations of the master virus seeds were conducted to ensure these viruses retained the previously identified attenuating determinants and phenotypes of the vaccine viruses. We also assessed vector competence of the vaccine viruses in sympatric (Thai) Aedes aegypti mosquito vectors.Conclusion/Significance:All four serotypes of master vaccine seeds retained the previously defined safety features, including all three major genetic loci of attenuation, small plaques, temperature sensitivity in mammalian cells, reduced replication in mosquito cell cultures, and reduced neurovirulence in new-born mice. In addition, the candidate vaccine viruses demonstrated greatly reduced infection and dissemination in Aedes aegypti mosquitoes, and are not likely to be transmissible by these mosquitoes. This manufacturing strategy has successfully been used to produce the candidate tetravalent vaccine, which is currently being tested in human clinical trials in the United States, Central and South America, and Asia. Source
Tarafdar P.K.,University of Hyderabad |
Vedantam L.V.,University of Hyderabad |
Vedantam L.V.,Shantha Biotechnics |
Podile A.R.,University of Hyderabad |
Swamy M.J.,University of Hyderabad
Harpins - a group of proteins that elicit hypersensitive response (HR) in non-host plants - are secreted by certain Gram-negative plant pathogenic bacteria upon interaction with the plant. In the present study, the microenvironment and solvent accessibility of the sole tryptophan residue (Trp-167) in harpin HrpZPss, secreted by Pseudomonas syringae pv. syringae, have been characterized by fluorescence spectroscopic studies. Emission λmax of the native protein at 328 nm indicates that Trp-167 is buried in a hydrophobic region in the interior of the protein matrix. Significant quenching (53%) was seen with the neutral quencher, acrylamide at 0.5 M concentration, whereas quenching by ionic quenchers, I- (∼10%) and Cs+ (negligible) was considerably lower. In the presence of 6.0 M guanidine hydrochloride (GdnHCl) the emission λmax shifted to 350.5 nm, and quenching by both neutral and ionic quenchers increased significantly, suggesting complete exposure of the indole side chain to the aqueous medium. Fluorescence studies on the thermal unfolding of HrpZPss are fully consistent with a complex thermal unfolding process and high thermal stability of this protein, inferred from previous differential scanning calorimetric and dynamic light scattering studies. However, the protein exhibits low resistance to chemical denaturants, with 50% unfolding seen in the presence of 1.77 M GdnHCl or 3.59 M urea. The ratio of m value, determined from linear extrapolation model, for GdnHCl and urea-induced unfolding was 1.8 and suggests the presence of hydrophobic interactions, which could possibly involve leucine zipper-like helical regions on the surface of the protein. © 2013 Elsevier Masson SAS. All rights reserved. Source
Bhattacharya S.K.,Indian National Institute of Cholera and Enteric Diseases |
Bhattacharya S.K.,Indian Council of Medical Research |
Sur D.,Indian National Institute of Cholera and Enteric Diseases |
Ali M.,Korean International Vaccine Institute |
And 19 more authors.
The Lancet Infectious Diseases
Background: Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. Methods: In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. Findings: 69 of 31932 recipients of vaccine and 219 of 34968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. Interpretation: Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Funding: Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. © 2013 Elsevier Ltd. Source
Shantha Biotechnics | Date: 2014-05-15
The invention describes a method of purifying polysaccharide protein conjugates using mixed mode chromatography. The method involves contacting a crude polysaccharide protein conjugate with a mixed mode resin comprising an inert porous shell and an activated core under conditions of low conductivity that allow binding of the contaminants and collecting the unbound polysaccharide protein conjugate in a flowthrough.
Crawled News Article
US-headquartered DiabetOmics Inc, a growth-stage medical diagnostics company with India operations, has raised its Series C round of funding worth $4 million from Ventureast to drive manufacturing and commercialisation in India, as per a company release. It has also raised an additional $1 million from KI Varaprasad Reddy, the founder of Shantha Biotechnics, who sold his company to Sanofi a few years ago. He will take over the post of chairman at DiabetOmics and will head the India unit once it is set up. DiabetOmics has developed a patented non-invasive, saliva-based glucose monitoring test for diabetes patients and an early detection test for gestational diabetes (in pregnant women) and pre-eclampsia (high blood pressure in pregnant women). The firm seeks to disrupt the market by doing away with the conventional diabetes monitoring process which involves a prick to get a small blood sample. This dissuades those suffering from diabetes and potential patients from testing their sample. The money raised will be invested to advance product development, obtain regulatory approvals in Europe, the US and in emerging markets and to set up a manufacturing facility in India and begin commercialisation. It plans to obtain CE Mark in 2015 and start commercialisation in India and several other countries in early 2016. Though it has not finalised a location for its manufacturing facility yet, it is evaluating options in Andhra Pradesh and Telangana, the newly carved state out of the south-eastern state of Andhra Pradesh. Srinivasa Nagalla, MD, president and CEO of DiabetOmics, said, “Lack of patient compliance with regular glucose monitoring is the primary cause of diabetes-related complications. We are looking to grow our presence in India to access Indian and SE-Asian markets.” Nagalla was previously founder and CEO of ProteoGenix, Inc., an innovator in maternal-fetal health diagnostics, which was acquired by Hologic, Inc. in 2010. Before founding ProteoGenix, he was associate professor of pediatrics at Oregon Health & Science University. He is the lead inventor on several key patents on biomarkers for clinical diagnostics, and has previously served on National Institutes of Health-sponsored national consortiums of biotechnology, genomics and proteomics. He has over 20 years of broad multi-disciplinary experience in clinical medicine, biotechnology, and commercialisation. Nagalla received his MD from the All-India Institute of Medical Sciences, New Delhi, and post-doctoral training at Harvard University and Oregon Health & Science University. Talking about the investment, Venkatadri Bobba, general partner of Ventureast, said, “An important focus area for us has been investing in companies fostering cutting-edge and breakthrough innovations in healthcare. We believe that DiabetOmics’ device is a game-changer and will definitely be successful in India.” This is DiabetOmics third round of funding. It has previously raised $15 million from Rogue Venture Partners, Dudley Foundation and government grants. Ventureast is a sector agnostic multi-stage VC firm with a special focus on healthcare. Ventureast’s Life Fund focuses on investments in cleantech, food & agriculture and healthcare sectors. It has previously made cross-border deals in drug discovery, medical devices, diagnostics, biotechnology and healthcare delivery. This is Ventureast’s third investment in tech healthcare space. Previously, it had invested in OneBreath, a startup that develops portable and rechargeable ventilators, and SmartRx that helps communication between doctor and patients after they are discharged.