Breaking News
May 27, 2018 - Study reveals striking disparities in health care access and quality across most nations
May 27, 2018 - The Yogi masters were right—meditation and breathing exercises can sharpen your mind
May 27, 2018 - SLU researcher aims to find solutions for diabetes patients at risk of hypoglycemia
May 27, 2018 - Scientists uncover the cause of insulin resistance in obesity
May 27, 2018 - $2.3 million NIH grant to support new project on oxytocin neurons and social behavior
May 27, 2018 - Less Driving Tied to Lower Cardiovascular Disease Risk
May 27, 2018 - Genetics Home Reference: LMNA-related congenital muscular dystrophy
May 27, 2018 - Long-term psychological study confirms time is the best medicine against homesickness
May 27, 2018 - Study explores if CPAP treatment can improve sexual QOL for sleep apnea patients
May 27, 2018 - Study investigates role played by brain in prosocial behavior
May 27, 2018 - New Guidelines Mean 1 in 3 Adults May Need Blood Pressure Meds
May 27, 2018 - Cerebrospinal Fluid (CSF) Analysis: MedlinePlus Lab Test Information
May 27, 2018 - Kids in tough neighborhoods head to ER more often
May 27, 2018 - Exercise alters brain’s dopamine system to help treat addiction, study finds
May 27, 2018 - Sepsis patients treated and released from ED for outpatient follow-up experience good outcomes
May 27, 2018 - Initiative cuts overuse of tests, treatments for bronchiolitis
May 27, 2018 - Study links ‘sleep spindles’ to memory reactivation
May 27, 2018 - Scientists develop new method to speed up genome evolution of baker’s yeast
May 27, 2018 - Sunscreen pills are fake says FDA
May 27, 2018 - Study finds increasing wealth gap between households of seniors and families with children
May 27, 2018 - Link between tuberculosis and Parkinson’s disease discovered
May 27, 2018 - Doctors call on health authorities for permission to provide stroke patients with life-saving treatment
May 26, 2018 - Couples who eat seafood-rich diet tend to get pregnant faster
May 26, 2018 - NIH summit presents recommendations to accelerate treatment development for Alzheimer’s disease
May 26, 2018 - Medication-related harm found to be common among older adults, but preventable
May 26, 2018 - Lunaphore and Vitro announce partnership to develop ISH protocols for RNA, DNA targets
May 26, 2018 - Cryoablation Efficacious for Cancer Pain, Review Finds
May 26, 2018 - Link between IBD and Parkinson’s might allow doctors to slow down condition
May 26, 2018 - Study finds fewer than 5% of low-income, urban mothers use prenatal vitamins before pregnancy
May 26, 2018 - California hospitals urge moms to favor breast milk over formula
May 26, 2018 - Most concussion patients do not receive follow-up care after hospital discharge, says study
May 26, 2018 - Lifetime risks of developing Alzheimer’s dementia vary by age, gender
May 26, 2018 - Researchers find novel ways to improve participation in clinical research
May 26, 2018 - Researchers develop methods for measuring free-base nicotine levels in e-cigarettes
May 26, 2018 - AHA: Preterm Birth Could Warn of Mom’s Future Heart Risks
May 26, 2018 - Some calories more harmful than others
May 26, 2018 - Study links cell size with commitment to division
May 26, 2018 - Researchers develop new, rapid blood test to detect liver damage
May 26, 2018 - Researchers discover cascade of immune processes linked to poor outcomes in aggressive breast cancer
May 26, 2018 - New research will use mathematics to solve mysteries in cell biology
May 26, 2018 - Proposed National Resilience Strategy to reverse catastrophic increases in ‘deaths of despair’
May 26, 2018 - Mice remain slim on burger diet
May 26, 2018 - BMC receives $13.5 million award to test methods for delivering childhood anxiety treatment
May 26, 2018 - ‘Right to Try Act’ will not benefit terminally-ill patients
May 26, 2018 - Study reveals novel statistical algorithm to identify potential disease genes
May 26, 2018 - Two genes play vital roles in malignant brain cancer
May 26, 2018 - Study explores link between groundwater lithium and diagnoses of bipolar disorder, dementia
May 26, 2018 - Researchers reveal stimulatory effects of myelin on young neural cells
May 26, 2018 - Small part of cellular protein that helps form long-term memories also drives neurodegeneration
May 26, 2018 - Four-legged friends can have heart issues, too
May 26, 2018 - Scientists create small, self-contained spaces inside mammalian cells
May 26, 2018 - Better Social Support Network Protects Black Men Against HIV
May 26, 2018 - National Heart, Lung, and Blood Institute (NHLBI)
May 26, 2018 - Burnout, depression can affect ophthalmology residents, study finds
May 26, 2018 - Latinos and African Americans more likely to experience serious depression than Whites
May 26, 2018 - Data from past epidemic could help improve response to future Ebola outbreaks
May 26, 2018 - Researchers provide insight into how the memory molecule limits brain plasticity
May 26, 2018 - OSU biologist describes ‘restoration ecology’ approach toward patient health
May 26, 2018 - New approach to study brown fat could aid in finding treatments for obesity
May 26, 2018 - UCI Center on Stress & Health receives NIH funding to develop digital health interventions
May 26, 2018 - Could More Fish in the Diet Boost Sex Lives and Fertility?
May 26, 2018 - NTU Singapore and SERI invent new scope to diagnose glaucoma
May 26, 2018 - Cancer cells co-opt pain-sensing ‘neural channel’ to increase tolerance against oxidative stress
May 26, 2018 - Study uncovers why pesticide exposure increases Parkinson’s disease risk in some people
May 26, 2018 - Study finds link between lead exposure and fertility rates
May 26, 2018 - Causes and treatment of acute heart failure vary by region, registry shows
May 26, 2018 - Delivery of standardized diabetes care could help achieve equitable health outcomes for all patients
May 26, 2018 - FDA authorizes marketing of OsteoDetect software for detecting wrist fractures
May 26, 2018 - HSE experts suggest new way of looking at infantilism
May 26, 2018 - Children and adolescents growing up in extreme societal conditions more likely to resort to violence
May 26, 2018 - New study puts forth most comprehensive tree of life for malaria parasites
May 26, 2018 - UVA researchers establish new guidelines for explorers of the submicroscopic world inside us
May 26, 2018 - Princeton Instruments and C-SOPS announce collaboration on innovative pharmaceutical technology
May 26, 2018 - New research shows why babies need to move in the womb
May 26, 2018 - UK steps forward to tackle global antimicrobial resistance
May 26, 2018 - CRISPR-Cas9-based strategy allows researchers to precisely alter hundreds of different genes
May 26, 2018 - Novoheart announces next generation of ‘Human heart-in-a-jar’ technology for advanced drug discovery
May 26, 2018 - UT Southwestern-led researchers find new way to determine prognosis of invasive kidney cancer
May 26, 2018 - Researchers develop film to prevent bacteria from growing on dental retainers and aligners
May 26, 2018 - Mobile health intervention for people with serious mental illness as effective as clinic-based treatment
Study paves new way for development of vaccines against epidemics

Study paves new way for development of vaccines against epidemics

image_pdfDownload PDFimage_print

The search for vaccines, treatments and preventive methods against infection by emerging viruses is one of the major challenges of global epidemiology. New pathological agents continue to emerge, such as the arbovirus transmitted by insects (in this case mosquitoes) that causes West Nile fever, named after being identified in Egypt, during the 1950s.

The disease affects thousands of people each year and is asymptomatic in 80% of cases. Roughly one in five infected people develops fever and other symptoms. In fewer than 1% of cases, especially among older people and children, the disease has significant neurological consequences, affecting the central nervous system, causing meningitis, encephalitis, and in extreme cases, an acute paralysis that leads to death. As yet, there are no vaccines against the virus.

First isolated in the West Nile District of Uganda in 1937, the disease did not have much epidemiological relevance until the 1990s. Carried by mosquito-infected migratory birds from Africa, the virus was spread through Europe from France to Russia. It reached North America in 1999 and has caused outbreaks in Canada (1999-2007), the United States (1999-2012) and Mexico (2003). Since then, more than 20,000 cases have been reported in North America, with almost 1,800 deaths.

“West Nile virus hasn’t reached Brazil, but it’s only a matter of time before it does,” said virologist Paolo Zanotto, head of the Molecular Evolution & Bioinformatics Laboratory (LEMB) at the University of São Paulo’s Biomedical Science Institute (ICB-USP) in Brazil. “How long will it take for migratory birds that spend the summer in North America to bring the virus to their winter refuges in Central America? West Nile virus is coming,” said the Brazilian investigator.

Hence the importance of a new study that has just been published, with Zanotto as one of its authors. By confirming that one of the acknowledged lineages of the virus – lineage eight – is not very virulent, the work points to the development of a vaccine within a few years: the relatively mild lineage 8 strains could theoretically “teach” the immune system to defend the organism against all lineages, especially the more widespread lineages 1 and 2, as well as 7, the most virulent.

The article is published in PLoS Neglected Tropical Diseases and is the result of collaboration among virologists at Institut Pasteur de Dakar in Senegal, the University of São Paulo and the Federal University of São Carlos, São Paulo State, Brazil. The study was supported by the Sao Paulo Research Foundation – FAPESP, Brazil’s National Council for Scientific & Technological Development (CNPq) and the European Union.

This immune defense strategy is similar to that used by flu vaccines, which combine the most recent strains of the influenza virus to combat the “flu of the year”, always caused by an emerging strain to which humans have not developed immunity.

Along with his PhD student Nicholas Di Paola, who has a scholarship from FAPESP, Zanotto is one of the authors of the article describing their study of the biological and phylogenetic characteristics of West African lineages of West Nile virus.

The principal investigators for the study were Di Paola and his Senegalese colleague Gamou Fall. Zanotto shared scientific responsibility for the research with Amadou Alpha Sall, scientific director of Institut Pasteur de Dakar.

Immunity against dangerous strains

In this study, three novel genes isolated from samples of the virus collected in West Africa by Di Paola and Fall were sequenced. The genes in question were representative of the most globally widespread lineage (1), the most virulent (7), and the least virulent (8).

Once sequenced, the genes were compared with the 862 West Nile virus gene sequences available from GenBank. Of these, 770 were lineage 1a from the Americas.

To reduce computer processing requirements, all lineage 1a sequences were removed, except for a single representative sequence. The researchers ended up with 95 sequences for phylogenetic analysis. The results included the discovery of two important traits of lineages 7 and 8.

In the case of lineage 8 (the least virulent), they detected substitution of the gene P122S, which induces mutations that may be linked to the lineage’s low replication rate and could, therefore, explain its low virulence.

“This is why lineage 8 would be ideal for a vaccine,” Zanotto said, adding that the development of a vaccine based on a virus with very low virulence would be capable of conferring immunity against the more dangerous lineages 1, 2 and 7 without the risk of producing symptoms of the disease.

In the case of lineage 7, the Brazilian and Senegalese virologists were able to identify a mutation (in gene S653F NS5) that is associated with an increased resistance to interferons, proteins made and released by the immune system’s white blood cells in response to the presence of viruses and other pathogens to interfere with their replication. This mutation could help explain the high virulence of lineage 7.

“With the exception of a single possible accidental infestation, which occurred in vitro in Africa, lineage 7 has never been isolated in humans,” Zanotto said. “But it was devastatingly lethal to mice in laboratory tests.”

The low virulence of lineage 8 and high virulence of lineage 7 were tested, confirmed and measured both in vitro, using infected cells, and in vivo, by inoculating mice in the Dakar laboratory. In the case of lineage 8, the virus displayed low capacity to replicate in vitro and almost no virulence in mice.

International cooperation in the fight against epidemics

The teams of virologists from USP and Senegal have a history of over 20 years of scientific collaboration, established on the basis of joint studies of dengue virus, the notorious Ebola, and more recently, Zika virus.

Outbreaks of these emerging viruses in Brazil and Senegal enabled ICB-USP and Institut Pasteur de Dakar to train professionals and learn the techniques required to become leading institutions in research on arboviruses (viruses transmitted by insects).

This leadership is reflected by the quantity and quality of the research conducted by the two institutions when the Zika outbreak was at its height in 2015. “The Dakar Pasteur and the team from USP published a larger number of relevant scientific papers on the subject in 2015 than even the researchers at the US Centers for Disease Control & Prevention (CDC),” Zanotto said.

Tagged with:

About author

Related Articles