scholarly journals Updates on Dengue Vaccine and Antiviral: Where Are We Heading?

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6768
Author(s):  
Harun Norshidah ◽  
Ramachandran Vignesh ◽  
Ngit Shin Lai
Keyword(s):  
Vaccine Development ◽  
Vaccine Candidate ◽  
Population Control ◽  
Antiviral Drug ◽  
Disease Monitoring ◽  
Dengue Vaccine ◽  
Vector Population ◽  
Novel Drugs ◽  
Dengue Prevention ◽  
Made In

Approximately 100–400 million people from more than 100 countries in the tropical and subtropical world are affected by dengue infections. Recent scientific breakthroughs have brought new insights into novel strategies for the production of dengue antivirals and vaccines. The search for specific dengue inhibitors is expanding, and the mechanisms for evaluating the efficacy of novel drugs are currently established, allowing for expedited translation into human trials. Furthermore, in the aftermath of the only FDA-approved vaccine, Dengvaxia, a safer and more effective dengue vaccine candidate is making its way through the clinical trials. Until an effective antiviral therapy and licensed vaccine are available, disease monitoring and vector population control will be the mainstays of dengue prevention. In this article, we highlighted recent advances made in the perspectives of efforts made recently, in dengue vaccine development and dengue antiviral drug.

scholarly journals Dengue Fever: Causes, Complications, and Vaccine Strategies

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Niyati Khetarpal ◽  
Ira Khanna
Keyword(s):  
Dengue Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Hemorrhagic Fever ◽  
Dengue Vaccine ◽  
Dengue Disease ◽  
The Public ◽  
Limited Application ◽  
Demographic Distribution ◽  
The Impact

Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through femaleAedesmosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur’s chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals.

Dengue and Zika Virus Infections Are Enhanced by Live Attenuated Dengue Vaccine but Not by Recombinant DSV4 Vaccine Candidate in Mouse Models

2020 ◽  
Author(s):  
Rahul Shukla ◽  
Julia A. Brown ◽  
Hemalatha Beesetti ◽  
Richa Ahuja ◽  
Viswanathan Ramasamy ◽  
...  
Keyword(s):  
Mouse Models ◽  
Zika Virus ◽  
Vaccine Candidate ◽  
Virus Infections ◽  
Dengue Vaccine

scholarly journals Analysis of cell-mediated immune responses in support of dengue vaccine development efforts

Vaccine ◽  
2015 ◽  
Vol 33 (50) ◽  
pp. 7083-7090 ◽  
Author(s):  
Alan L. Rothman ◽  
Jeffrey R. Currier ◽  
Heather L. Friberg ◽  
Anuja Mathew
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Dengue Vaccine

scholarly journals Overview of Plant-Derived Vaccine Antigens: Dengue Virus

2011 ◽  
Vol 14 (3) ◽  
pp. 400 ◽  
Author(s):  
Ravindra B Malabadi ◽  
Advaita Ganguly ◽  
Jaime A Teixeira da Silva ◽  
Archana Parashar ◽  
Mavanur R Suresh ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Dengue Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Low Cost ◽  
Current Status ◽  
Human Immune Deficiency Virus ◽  
Dengue Vaccine ◽  
New Methods ◽  
Vaccine Antigens

ABSTRACT - This review highlights the advantages and current status of plant-derived vaccine development with special reference to the dengue virus. There are numerous problems involved in dengue vaccine development, and there is no vaccine against all four dengue serotypes. Dengue vaccine development using traditional approaches has not been satisfactory in terms of inducing neutralizing antibodies. Recently, these issues were addressed by showing a very good response to inducing neutralizing antibodies by plant-derived dengue vaccine antigens. This indicates the feasibility of using plant-derived vaccine antigens as a low-cost method to combat dengue and other infectious diseases. The application of new methods and strategies such as dendritic cell targeting in cancer therapy, severe acute respiratory syndrome, tuberculosis, human immune deficiency virus, and malaria might play an important role. These new methods are more efficient than traditional protocols. It is expected that in the near future, plant-derived vaccine antigens or antibodies will play an important role in the control of human infectious diseases. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Two Complex, Adenovirus-Based Vaccines That Together Induce Immune Responses to All Four Dengue Virus Serotypes

2006 ◽  
Vol 14 (2) ◽  
pp. 182-189 ◽  
Author(s):  
David H. Holman ◽  
Danher Wang ◽  
Kanakatte Raviprakash ◽  
Nicholas U. Raja ◽  
Min Luo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Vaccine Development ◽  
De Novo ◽  
Natural Infection ◽  
Hemorrhagic Fever ◽  
Virus Infections ◽  
Dengue Vaccine ◽  
Membrane Antigens ◽  
Dengue Virus Serotypes

ABSTRACT Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

scholarly journals The research significance of concomitant use of CAR-CD138-NK and CAR-CD19-NK to target multiple myelomas

2018 ◽  
Vol 16 ◽  
pp. 205873921878896 ◽  
Author(s):  
Songbo Zhao ◽  
Zhichao Han ◽  
Cheng Ji ◽  
Gangli An ◽  
Huimin Meng ◽  
...  
Keyword(s):  
Nk Cells ◽  
Lymphoblastic Leukemia ◽  
Small Subset ◽  
Novel Drugs ◽  
Prevalent Disease ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Multiple Myelomas ◽  
Made In

Multiple myeloma (MM) is a type of cancer characterized by abnormal proliferation of clonal cells; it is the very dangerous and highly prevalent disease. Although significant progress has been made in clinical research, especially with novel drugs such as bortezomib, lenalidomide, and carfilzomib, most of the patients with MM still suffer from often fetal relapses due to drug resistance. In this study, we aimed to develop immune cells that could specifically target and destroy MM cells. Chimeric antigen receptor–modified NK-92 (CAR-NK92) cells have been very effective against B-cell acute lymphoblastic leukemia (B-ALL); as MM shows high expression of CD138, we constructed CD138-directed CAR-NK-92MI cells (CAR-CD138). It 2is reported that there is a small subset of CD138–/CD19+ MM cells showing, to some extent, stem cell qualities. We therefore generated the CD19-directed CAR-NK-92MI cells (CAR-CD19) as well. These two CAR-NK cells showed strong in vitro biological activity in specifically killing target tumor cells. Thus, the concomitant use of these CAR-NK cells may achieve excellent results in vivo.

scholarly journals Cleaning up Third World Debt Without Getting Taken to the Cleaners

1990 ◽  
Vol 4 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Jeremy Bulow ◽  
Kenneth Rogoff
Keyword(s):  
Third World ◽  
Debt Crisis ◽  
Population Control ◽  
Development Aid ◽  
Bank Debt ◽  
International Debt ◽  
Regulatory Changes ◽  
Loan Guarantees ◽  
Third World Debt ◽  
Made In

Should taxpayers of wealthy countries finance a leveraged buyout of third world debt? The case for establishing an international debt discount facility rests on the belief that the overhang of foreign commercial bank debt is stifling growth in the Highly Indebted Countries, and that coordination problems among private sector banks are blocking efficiency-enhancing debt reduction schemes. Thus there is scope for a multilateral government agency to step in, buy up the debts, and pass on the efficiency gains to struggling debtors. Our contention is that a debt discount facility would in fact be a black hole for aid funds, and would yield only minimal efficiency benefits. Our assessment of the debt crisis suggests a very different approach. Development aid should be divorced from debt negotiations and instead should be tied to countries' performance in areas such as environmental policy, drug interdiction, and population control. Future aid allocations should not be disguised as loan guarantees, and the massive bond obligations of existing multilateral lenders ought to be placed on the books. Finally, we recommend reversing a number of legal and regulatory changes made in the 1970s that served to encourage the loans in the first place.

Surface-associated and secreted factors ofStreptococcus suisin epidemiology, pathogenesis and vaccine development

2009 ◽  
Vol 10 (1) ◽  
pp. 65-83 ◽  
Author(s):  
Christoph Georg Baums ◽  
Peter Valentin-Weigand
Keyword(s):  
Vaccine Development ◽  
Current Knowledge ◽  
Swine Industry ◽  
Major Health Problem ◽  
Major Health ◽  
Secreted Factors ◽  
Diverse Species ◽  
Virulent Strains ◽  
Enormous Amount ◽  
Made In

AbstractStreptococcus suisis an invasive porcine pathogen associated with meningitis, arthritis, bronchopneumonia and other diseases. The pathogen constitutes a major health problem in the swine industry worldwide. Furthermore,S. suisis an important zoonotic agent causing meningitis and other diseases in humans exposed to pigs or pork. Current knowledge on pathogenesis is limited, despite the enormous amount of data generated by ‘omics’ research. Accordingly, immunprophylaxis (in pigs) is hampered by lack of a cross-protective vaccine against virulent strains of this diverse species. This review focuses on bacterial factors, both surface-associated and secreted ones, which are considered to contribute toS. suisinteraction(s) with host factors and cells. Factors are presented with respect to (i) their identification and features, (ii) their distribution amongS. suisand (iii) their significance for virulence, immune response and vaccination. This review also shows the enormous progress made in research onS. suisover the last few years, and it emphasizes the numerous challenging questions remaining to be answered in the future.

scholarly journals Engineering a Live Attenuated Porcine Epidemic Diarrhea Virus Vaccine Candidate via Inactivation of the Viral 2'-O-Methyltransferase and the Endocytosis Signal of the Spike Protein

2019 ◽  
Vol 93 (15) ◽  
Author(s):  
Yixuan Hou ◽  
Hanzhong Ke ◽  
Jineui Kim ◽  
Dongwan Yoo ◽  
Yunfang Su ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Spike Protein ◽  
Economic Losses ◽  
High Dose ◽  
Type I ◽  
Viral Pathogen ◽  
Diarrhea Virus ◽  
Porcine Epidemic Diarrhea

ABSTRACT Porcine epidemic diarrhea virus (PEDV) causes high mortality in neonatal piglets; however, effective and safe vaccines are still not available. We hypothesized that inactivation of the 2′-O-methyltransferase (2′-O-MTase) activity of nsp16 and the endocytosis signal of the spike protein attenuates PEDV yet retains its immunogenicity in pigs. We generated a recombinant PEDV, KDKE4A, with quadruple alanine substitutions in the catalytic tetrad of the 2′-O-MTase using a virulent infectious cDNA clone, icPC22A, as the backbone. Next, we constructed another mutant, KDKE4A-SYA, by abolishing the endocytosis signal of the spike protein of KDKE4A. Compared with icPC22A, the KDKE4A and KDKE4A-SYA mutants replicated less efficiently in vitro but induced stronger type I and type III interferon responses. The pathogenesis and immunogenicities of the mutants were evaluated in gnotobiotic piglets. The virulence of KDKE4A-SYA and KDKE4A was significantly reduced compared with that of icPC22A. Mortality rates were 100%, 17%, and 0% in the icPC22A-, KDKE4A-, and KDKE4A-SYA-inoculated groups, respectively. At 21 days postinoculation (dpi), all surviving pigs were challenged orally with a high dose of icPC22A. The KDKE4A-SYA- and KDKE4A-inoculated pigs were protected from the challenge, because no KDKE4A-SYA- and one KDKE4A-inoculated pig developed diarrhea whereas all the pigs in the mock-inoculated group had severe diarrhea, and 33% of them died. Furthermore, we serially passaged the KDKE4A-SYA mutant in pigs three times and did not find any reversion of the introduced mutations. The data suggest that KDKE4A-SYA may be a PEDV vaccine candidate. IMPORTANCE PEDV is the most economically important porcine enteric viral pathogen and has caused immense economic losses in the pork industries in many countries. Effective and safe vaccines are desperately required but still not available. 2′-O-MTase (nsp16) is highly conserved among coronaviruses (CoVs), and the inactivation of nsp16 in live attenuated vaccines has been attempted for several betacoronaviruses. We show that inactivation of both 2′-O-MTase and the endocytosis signal of the spike protein is an approach to designing a promising live attenuated vaccine for PEDV. The in vivo passaging data also validated the stability of the KDKE4A-SYA mutant. KDKE4A-SYA warrants further evaluation in sows and their piglets and may be used as a platform for further optimization. Our findings further confirmed that nsp16 can be a universal target for CoV vaccine development and will aid in the development of vaccines against other emerging CoVs.

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