Case report: Regression of Glioblastoma after flavivirus infection.

Glioblastoma is the most frequent and aggressive primary brain cancer. In preclinical studies, Zika virus, a flavivirus that triggers the death of glioblastoma stem-like cells. However, the flavivirus oncolytic activity has not been demonstrated in human patients.

Evaluation of Two Adjuvant Formulations for an Inactivated Yellow Fever 17DD Vaccine Candidate in Mice.

The attenuated yellow fever (YF) vaccine is one of the most successful vaccines ever developed. After a single dose administration YF vaccine can induce balanced Th1/Th2 immune responses and long-lasting neutralizing antibodies. These attributes endorsed it as a model of how to properly stimulate the innate response to target protective immune responses.

Safety and immunogenicity of 17DD attenuated yellow fever vaccine in howler monkeys (Alouatta spp.).

Background: Alouatta spp. are highly susceptible to yellow fever (YF) infection and develop an often fatal disease. The threat posed by an outbreak started in 2016 leads us to investigate vaccination as a potential tool in preventing YF in non-human primates (NHP).

Purification of yellow fever virus produced in Vero cells for inactivated vaccine manufacture.

Yellow fever (YF) is a high-lethality viral disease, endemic in tropical regions of South America and Africa, with a population of over 900 million people under risk. A highly effective attenuated vaccine, produced in embryonated eggs, has been used for about 80 years. However, egg-based production limits manufacturing capacity, and vaccine shortage led to the emergency use of a fractional dose (1/5) by the WHO in an outbreak in Africa in 2016 and by Brazilian authorities during an outbreak in 2018.

Detection of post-vaccination enhanced dengue virus infection in macaques: An improved model for early assessment of dengue vaccines.

The need for improved dengue vaccines remains since the only licensed vaccine, Dengvaxia, shows variable efficacy depending on the infecting dengue virus (DENV) type, and increases the risk of hospitalization for severe dengue in children not exposed to DENV before vaccination. Here, we developed a tetravalent dengue purified and inactivated vaccine (DPIV) candidate and characterized, in rhesus macaques, its immunogenicity and efficacy to control DENV infection by analyzing, after challenge, both viral replication and changes in biological markers associated with dengue in humans. Although DPIV elicited cross-type and long-lasting DENV-neutralizing antibody responses, it failed to control DENV infection.

Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques.

The macaque is widely accepted as a suitable model for preclinical characterization of dengue vaccine candidates. However, the only vaccine for which both preclinical and clinical efficacy results were reported so far showed efficacy levels that were substantially different between macaques and humans. We hypothesized that this model's predictive capacity may be improved using recent and minimally passaged dengue virus isolates, and by assessing vaccine efficacy by characterizing not only the post-dengue virus challenge viremia/RNAemia but also the associated-cytokine profile.

Plant-Produced Subunit Vaccine Candidates against Yellow Fever Induce Virus Neutralizing Antibodies and Confer Protection against Viral Challenge in Animal Models.

Yellow fever (YF) is a viral disease transmitted by mosquitoes and endemic mostly in South America and Africa with 20-50% fatality. All current licensed YF vaccines, including YF-Vax (Sanofi-Pasteur, Lyon, France) and 17DD-YFV (Bio-Manguinhos, Rio de Janeiro, Brazil), are based on live attenuated virus produced in hens' eggs and have been widely used. The YF vaccines are considered safe and highly effective.

An inactivated yellow fever 17DD vaccine cultivated in Vero cell cultures.

Yellow fever is an acute infectious disease caused by prototype virus of the genus Flavivirus. It is endemic in Africa and South America where it represents a serious public health problem causing epidemics of hemorrhagic fever with mortality rates ranging from 20% to 50%. There is no available antiviral therapy and vaccination is the primary method of disease control.

Voices from the front lines. Four leaders on the cross-border challeng they've faced.

Executives on the front lines of managing across borders share their insights: Luc Minguet, of France's Michelin, talks about the importance of cultural training not just for managers taking on assignments abroad but also for local employees who work with colleagues from around the world. He describes how his own experience learning to communicate across cultures reflects the tire-maker's broader practices. Eduardo Caride, of Madrid-based Telefónica, explains how the relatively young multinational is investing in a diverse talent mix as it strives to become a truly global company.

Development of a membrane adsorber based capture step for the purification of yellow fever virus.

Yellow fever (YF) is an endemic disease in some tropical areas of South America and Africa that presents lethality rate between 20 and 50%. There is no specific treatment and to control this disease a highly effective live-attenuated egg based vaccine is widely used for travelers and residents of areas where YF is endemic. However, recent reports of rare, sometimes fatal, adverse events post-vaccination have raised concerns.

Evidence for interferon production and its correlation with YF 17DD vaccine virus yields in primary chick embryo cells.

Early experiments have resulted in the establishment of an efficient methodology for the production of a yellow fever vaccine in chicken embryo fibroblasts (CEF) using the 17DD virus strain [Freire, M.S., Mann, G.

Limited replication of yellow fever 17DD and 17D-Dengue recombinant viruses in rhesus monkeys.

For the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. We have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17DD virus (YFV 17DD) and recombinant yellow fever 17D viruses expressing envelope proteins of dengue virus serotypes 2 and 4 (17D-DENV-2 and 17D-DENV-4). Serum samples from rhesus monkeys inoculated with YFV 17DD and 17D-DENV chimeras by intracerebral or subcutaneous route were used to determine and compare the viremia induced by these viruses.

Pressure-inactivated yellow fever 17DD virus: implications for vaccine development.

The successful Yellow Fever (YF) vaccine consists of the live attenuated 17D-204 or 17DD viruses. Despite its excellent record of efficacy and safety, serious adverse events have been recorded and influenced extensive vaccination in endemic areas. Therefore, alternative strategies should be considered, which may include inactivated whole virus.

Study of the genetic stability of measles virus CAM-70 vaccine strain after serial passages in chicken embryo fibroblasts primary cultures.

To evaluate the genetic stability of the CAM-70 measles vaccine strain we have performed 10 serial passages of the seed lot virus FMS-7 in chicken embryo fibroblasts primary cultures (CEF) under production conditions. The nucleotide sequences of the seed lot virus, the virus from a vaccine vial (third passage) and from the 10th passage were determined and compared with each other and with sequences from other sources. The full genome analysis of the CAM-70 vaccine still considers it as the most divergent among all vaccine strains.

Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys.

Among the flaviviruses, dengue, with its four serotypes, has spread throughout the tropics. The most advanced vaccines developed so far include live attenuated viruses, which have been tested in humans but none has been licensed. Preclinical testing of dengue vaccine candidates is performed initially in mice and in nonhuman primates.

Construction and biological properties of yellow fever 17D/dengue type 1 recombinant virus.

Dengue virus, a mosquito-borne flavivirus, is one of the most formidable public health threats in tropical and subtropical regions. As yet, there is no licensed vaccine to protect against the disease. A chimeric yellow fever (YF) 17D/dengue (DEN) type 1 virus was constructed by replacing the pre-membrane and envelope genes of YF 17D virus with those from DEN 1 VeMir95 virus, a Venezuelan isolate.

Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys.

A chimeric yellow fever (YF)-dengue serotype 2 (dengue 2) virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus.

Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy.

Background: Antiretroviral therapy is provided by the Brazilian Ministry of Health to eligible HIV-infected individuals. Based on clinical and immunological classification, the Brazilian guidelines recommend dual or triple therapy for children. However, the development of drug-resistant strains or poor adherence to therapy could impact the efficacy of this approach.

Genotypic and phenotypic evidence of different drug-resistance mutation patterns between B and non-B subtype isolates of human immunodeficiency virus type 1 found in Brazilian patients failing HAART.

We have investigated the phenotypic and genotypic susceptibility of 14 HIV-1 strains isolated from individuals failing HAART therapy to protease inhibitors (PI). Proviral and plasma viral pol gene fragment were amplified, sequenced and subtyped. Nine samples clustered with protease subtype B reference strains and the remaining samples were classified as non-B subtype corresponding to subtype F (n = 4) and subtype A (n = 1).

Sexual transmission of HIV-1 isolate showing G-->A hypermutation.

Retroviral genomes with a high frequency of G-->A mutations are thought to originate during reverse transcription (RT). Here we present a case report of an AIDS patient infected with a subtype F variant where extensive G-->A hypermutation (G-->A Hypm) sequences were found in the protease gene. This patient was failing HAART at the time the hypermutation was found.

Genetic variability of HIV-1 protease from Nigeria and correlation with protease inhibitors drug resistance.

In Nigeria, the most populous country in Africa, the characterization of HIV-1 strains has been limited. In this study we evaluated the genetic diversity of the protease coding region, one of the anti-retroviral therapy target, and investigated the presence of mutations related to resistance to HIV protease inhibitors. We analyzed samples collected during 1996 and all patients were anti-retroviral drug naïves.

Drug-resistant reverse transcriptase genotyping and phenotyping of B and non-B subtypes (F and A) of human immunodeficiency virus type I found in Brazilian patients failing HAART.

Development of drug resistance is the inevitable consequence of incomplete suppression of virus plasma levels in HIV-1-infected patients treated with highly active antiretroviral therapy. Resistance mutations previously characterized have been found in B subtype viruses of developed countries. Moreover, mutation profiles for non-B and more divergent B subtype viruses found in developing countries shall be analyzed together with their ex vivo phenotyping in order to establish an exact correlation between the genotyping data and the clinical management counseling for those uncommon virus subtypes.

Comparison between site-specific DNA binding proteins of male and female Schistosoma mansoni.

Several amplicons with approximately 120 bp each, obtained from the upstream domain of Schistosoma mansoni female-specific gene F-10, were coupled to Dynabeads M-280 streptavidin. The beads were used as a matrix for affinity purification of nuclear proteins obtained from mixed populations of adult worms. A protein of approximately 12 kDa, bound to the DNA in a sequence-independent manner.

Sequence diversity of the reverse transcriptase of human immunodeficiency virus type 1 from untreated Brazilian individuals.

The presence of human immunodeficiency virus type 1 (HIV-1) bearing mutations resistant to nucleosidic inhibitors of the viral reverse transcriptase (RT) derived from HIV-seropositive asymptomatic and untreated volunteer blood donors was examined. The RT amplicons of 32 specimens were analyzed by using a reverse hybridization line probe assay technique that detects resistance against zidovudine (3'-azido-3'-deoxythymidine [AZT], didanosine (2',3'-dideoxyinosine [ddI], zalcitabine (2',3'-dideoxycytidine [ddC]), and lamivudine ((-)-beta-L-2',3'-dideoxy-3'-thiacytidine [3TC]) at amino acid positions 41, 69, 70, 74, 184, and 215 of the HIV RT. One sample (brp004, subtype B) showed an AZT resistance secondary mutation at position K70R.

Molecular aspects of Schistosoma mansoni female maturation.

Incubation of total protein extracts of Schistosoma mansoni with 3H 17-beta-estradiol and 20-hydroxyecdysone, revealed steroid binding proteins in both, male and female worms. The interaction of nuclear proteins with restriction fragments of the gender and stage-specific gene F-10 was investigated using the "Band-Shift" technique. Distinct male and female nuclear proteins bound to the fragments of this gene.