A Multi-Perspective Review on Dengue Research.

Dengue fever is a disease which is caused by a family of viruses named Flaviviridae which are transmitted by female Aedes mosquitoes. Today, this is endemic in more than 100 nations in the World Health Organization's African, Americas, Eastern Mediterranean, South-East Asia and Western Pacific locales. The treatment of typical dengue is focused on relieving the symptoms and signs. Carica papaya is a very common plant whose leaf extract is used in the treatment of this disease. Despite extensive research on Dengue, not a single vaccine or anti-viral drug was available until 2016 (a partially effective Chimeric Yellow fever virus treated by DENV-Tetravalent Dengue Vaccine for dengue fever made by Sanofi Pasteur). This review highlights dengue fever's current situation and explains the importance of Natural chemical moieties like methionine-proline anilides, tetrapeptide aldehyde uncovered via Structure Activity Relationship studies. Also, we have reviewed the drug candidates currently in the clinical trials that have the potential to solve these issues. Important patents in the past 20 years have been outlined in this review. An in depth Protein Data Bank analysis of the different possible target proteins that can potentially have a major role in curing Dengue fever has been conducted.

Immunogenicity and Protection After Vaccination With a Modified Vaccinia Virus Ankara-Vectored Yellow Fever Vaccine in the Hamster Model.

The highly efficacious live-attenuated 17D yellow fever (YF) vaccine is occasionally associated with rare life-threatening adverse events. Modified vaccinia virus Ankara (MVA), a non-replicating poxvirus, has been used as a vaccine platform to safely deliver various antigens. A MVA-based YF vaccine (MVA-BN-YF) was tested with and without a non-mineral oil adjuvant in a hamster model of lethal YF disease and protective efficacy of this vaccine was compared with the 17D vaccine. The vaccine candidate MVA-BN-YF generated a protective response in hamsters infected with YFV that was comparable to protection by the live 17D vaccine. Similar levels of neutralizing antibody were observed in animals vaccinated with either vaccine alone or vaccine with adjuvant. Significant improvement in survival, weight change, and serum alanine aminotransferase levels were observed in vaccinated hamsters when administered 42 and 14 days prior to challenge with Jimenez YF virus (YFV). Neutralizing antibodies induced by MVA-BN-YF were transferred to naïve hamsters prior to virus challenge. Passive administration of neutralizing antibody 24 h prior to virus infection resulted in significantly improved survival and weight change. A trend toward reduced liver enzyme levels was also observed. MVA-BN-YF, therefore, represents a safe alternative to vaccination with live-attenuated YFV.

In vitro and in vivo antiviral properties of sulfated galactomannans against yellow fever virus (BeH111 strain) and dengue 1 virus (Hawaii strain).

Two galactomannans, one extracted from seeds of Mimosa scabrella, having a mannose to galactose ratio of 1.1, and another with a 1.4 ratio from seeds of Leucaena leucocephala, were sulfated. The products from M. scabrella (BRS) and L. leucocephala (LLS) had a degree of sulfation of 0.62 and 0.50, and an average molecular weight of 620x10(3) and 574x10(3) gmol(-1), respectively. Their activities against yellow fever virus (YFV; BeH111 strain) and dengue 1 virus (DEN-1; Hawaii strain) were evaluated. This was carried out in young mice following intraperitoneal infection with YFV. At a dose of 49 mgkg(-1), BRS and LLS gave protection against death in 87.7 and 96.5% of the mice, respectively. When challenged with 37.5 LD50 of YFV, mice previously inoculated with BRS+virus or LLS+virus, showed 93.3 and 100% resistance, respectively, with neutralization titers similar to mice injected with 25 LD50 of formaldehyde-inactivated YFV. In vitro experiments with YFV and DEN-1 in C6/36 cell culture assays in 24-well microplates showed that concentrations that produced a 100-fold decrease in virus titer of YFV were 586 and 385 mgl(-1) for BRS and LLS, respectively. For DEN-1 they were 347 and 37 mgl(-1), respectively. Sulfated galactomannans, thus demonstrate in vitro and in vivo activity against flaviviruses.

Recombinant, chimaeric live, attenuated vaccine (ChimeriVax) incorporating the envelope genes of Japanese encephalitis (SA14-14-2) virus and the capsid and nonstructural genes of yellow fever (17D) virus is safe, immunogenic and protective in non-human primates.

Yellow fever 17D virus, a safe and effective live, attenuated vaccine, was used as a vector for genes encoding the protective antigenic determinants of a heterologous member of the genus Flavivirus, Japanese encephalitis (JE) virus, the leading cause of acute viral central nervous system infection and death throughout Asia. The viral envelope (prM and E) genes of a full-length cDNA clone of YF 17D virus were replaced with the corresponding genes of JE SA14-14-2, a strain licensed as a live, attenuated vaccine in China. Full-length RNA transcripts of the YF/JE chimaera were used to transfect Vero cells. The progeny virus (named 'ChimeriVax-JE'), was used to define safety after intracerebral (i.c.) inoculation of rhesus monkeys. Monkeys (N = 3) inoculated with a high dose (6.6 log10 pfu) developed a brief viremia, showed no signs of illness, developed high titers of anti-JE neutralizing antibody, and had minimal brain and spinal cord lesion scores according to criteria specified in the WHO monkey neurovirulence test. A control group of 3 monkeys that received a lower dose (4.2 log10 pfu) of commercial YF 17D vaccine had slightly higher lesion scores. To develop a lethal monkey model of JE for vaccine protection tests, we inoculated groups of monkeys i.c. or intranasally (i.n.) with a JE virus strain found to be highly neurovirulent and neuroinvasive for mice. Monkeys inoculated i.c., but not i.n., developed severe encephalitis after an incubation period of 8-13 days. The ChimeriVax-JE virus was passed in a cell line acceptable for human use (diploid fetal rhesus lung) and 4.3 or 5.3 log10 pfu were inoculated into groups of 3 monkeys by the subcutaneous route. All 6 animals developed brief viremias (peak titer < 2.0 log10 pfu/ml) and subsequently had anti-JE but no yellow fever neutralizing antibodies. On day 64, the monkeys were challenged i.c. with 5.5 log10 pfu of virulent JE virus. The immunized animals had no detectable viremia post-challenge, whereas 4 unimmunized controls became viremic. Only 1 of 6 (17%) vaccinated monkeys but 4 of 4 (100%) unvaccinated controls developed encephalitis. Histopathological examination 30 days after challenge confirmed that the protected, immunized animals had no or minimal evidence of encephalitis. These data demonstrated the ability of the ChimeriVax-JE to induce a rapid humoral immune response and to protect against a very severe, direct intracerebral virus challenge. Target areas of neuronal damage and inflammation in monkeys infected IC with wild-type JE, the chimaeric virus and YF 17D were similar, indicating that the histopathological scoring system used for the WHO yellow fever monkey neurovirulence test will be applicable to control testing of chimaeric seed viruses and vaccines.

[Combined (associated) vaccination against quarantinable infections]. / Kompleksnaia (assotsiirovannaia) vaktsinatsiia protiv karantinnykh infektsii.

The presence of several active foci of infection of different etiology is an indication for complex (combined) immunization against these diseases. The scheme of complex (combined) immunization against plague, cholera and yellow fever has been experimentally substantiated and successfully tested on volunteers.