Nav: Home

Research paves the way for the development of vaccines for emerging viruses

January 30, 2018

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.
-end-
About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. For more information: http://www.fapesp.br/en.

Fundação de Amparo à Pesquisa do Estado de São Paulo

Related West Nile Virus Articles:

West Nile virus in the New World: Reflections on 20 years in pursuit of an elusive foe
Though eradication of West Nile virus remains beyond our capability, the body of knowledge built since its arrival in the Americas in 1999 is now powering efforts to minimize its impact and prepare for the invasion of other mosquito-borne diseases.
Light pollution may be increasing West Nile virus spillover from wild birds
House sparrows infected with West Nile virus (WNV) that live in light polluted conditions remain infectious for two days longer than those who do not, increasing the potential for a WNV outbreak by about 41%.
Fifteen years of mosquito data implicate species most likely to transmit West Nile virus in Iowa
A study published this week that analyzed 15 years of mosquito surveillance data shows Iowa's western counties experience a higher abundance of the species thought to most commonly carry West Nile virus.
Mount Sinai researchers find significant delays in West Nile virus reporting
Mount Sinai researchers found significant delays in reporting human cases of West Nile virus, hampering real-time forecasting of the potentially deadly mosquito-borne disease, according to a study in the JAMA Network Open in April.
Insecticide resistance genes affect vector competence for West Nile virus
In a context of overuse of insecticides, which leads to the selection of resistant mosquitoes, it is already known that this resistance to insecticides affects interactions between mosquitoes and the pathogens they transmit.
Where will the world's next Zika, West Nile or Dengue virus come from?
Scientists from the University of California, Davis, have identified wildlife species that are the most likely to host flaviviruses such as Zika, West Nile, dengue and yellow fever.
Vanderbilt discovery could neutralize West Nile virus
Researchers at Vanderbilt University Medical Center and colleagues have isolated a human monoclonal antibody that can 'neutralize' the West Nile virus and potentially prevent a leading cause of viral encephalitis (brain inflammation) in the United States.
West Nile virus reemerged and spread to new areas in Greece in 2017, researchers show
West Nile virus (WNV), which is transmitted via mosquito bites, reemerged and spread to new territories of Greece in 2017 following a two-year hiatus in reported human cases, according to findings presented at the 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).
Researchers develop a novel RNA-based therapy to target West Nile virus
A Yale-led research team developed a new RNA therapy, delivered through the nose, to treat mice infected with West Nile Virus.
Like Zika, West Nile virus causes fetal brain damage, death in mice
Two viruses closely related to Zika -- West Nile and Powassan -- can spread from an infected pregnant mouse to her fetuses, causing brain damage and fetal death, according to a new study from Washington University School of Medicine in St.
More West Nile Virus News and West Nile Virus Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.