Newer variant of COVID-19-causing virus dominates global infections

Newer variant of COVID-19

Research out today in the journal Cell shows that a specific change in the SARS-CoV-2 coronavirus virus genome, previously associated with increased viral transmission and the spread of COVID-19, is more infectious in cell culture. The variant in question, D614G, makes a small but effective change in the virus's 'Spike' protein, which the virus uses to enter human cells.

Bette Korber, a theoretical biologist at Los Alamos National Laboratory and lead author of the study, noted, "The D614G variant first came to our attention in early April, as we had observed a strikingly repetitive pattern. All over the world, even when local epidemics had many cases of the original form circulating, soon after the D614G variant was introduced into a region it became the prevalent form."

Geographic information from samples from the GISAID COVID-19 viral sequence database enabled tracking of this highly recurrent pattern, a shift in the viral population from the original form to the D614G variant. This occurred at every geographic level: country, subcountry, county, and city.

Two independent lines of experimental evidence that support these initial results are included in today's paper. These additional experiments, led by Professor Erica Ollmann Saphire, Ph.D., at the La Jolla Institute, and by Professor David Montefiori, Ph.D., at Duke University, showed that the D614G change increases the virus's infectivity in the laboratory. These new experiments, as well as more extensive sequence and clinical data and improved statistical models, are presented in the Cell paper. More in vivo work remains to be done to determine the full implications of the change.

The SARS-CoV-2 virus has a low mutation rate overall (much lower than the viruses that cause influenza and HIV-AIDS). The D614G variant appears as part of a set of four linked mutations that appear to have arisen once and then moved together around the world as a consistent set of variations.

"It's remarkable to me," commented Will Fischer of Los Alamos, an author on the study, "both that this increase in infectivity was detected by careful observation of sequence data alone, and that our experimental colleagues could confirm it with live virus in such a short time."

Fortunately, "the clinical data in this paper from Sheffield showed that even though patients with the new G virus carried more copies of the virus than patients infected with D, there wasn't a corresponding increase in the severity of illness," said Saphire, who leads the Gates Foundation-supported Coronavirus Immunotherapy Consortium (CoVIC).

Korber noted, "These findings suggest that the newer form of the virus may be even more readily transmitted than the original form -- whether or not that conclusion is ultimately confirmed, it highlights the value of what were already good ideas: to wear masks and to maintain social distancing."

Research partners from Los Alamos National Laboratory, Duke University, and the University of Sheffield initially published work on this analysis on the bioRxiv site in an April 2020 preprint. That work also included observations of COVID-19 patients from Sheffield that suggested an association of the D614G variant with higher viral loads in the upper respiratory tract.

"It is possible to track SARS-CoV-2 evolution globally because researchers worldwide are rapidly making their viral sequence data available through the GISAID viral sequence database," Korber said. Currently tens of thousands of sequences are available through this project, and this enabled Korber and the research team to identify the emergence of the D614G variant.

GISAID was established to encourage collaboration among influenza researchers, but early in the epidemic the consortium established a SARS-CoV-2 database, which soon became the de facto standard for sharing outbreak sequences among researchers worldwide.

The study, "Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus" was supported by the Medical Research Council (MRC) part of UK Research & Innovation (UKRI the National Institute of Health Research (NIHR); Genome Research Limited, operating as the Wellcome Sanger Institute; CoVIC, INV-006133 of the COVID-19 Therapeutics Accelerator, supported by the Bill and Melinda Gates Foundation, Mastercard, Wellcome; private philanthropic support, as well as the Overton family; a FastGrant, from Emergent Ventures, in aid of COVID-19 research; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Interagency Agreement No. AAI12007-001-00000, and the Los Alamos Laboratory Directed Research and Development program.

Additional study authors included S. Gnanakaran, H. Yoon, J. Theiler, W. Abfalterer, N. Hengartner, E.E. Giorgi, T. Bhattacharya, B. Foley, K.M. Hastie, M.D. Parker, D.G. Partridge, C.M. Evans, T.M. Freeman, T.I. de Silva, C. McDanal, L.G. Perez, H. Tang, A. Moon-Walker, S.P. Whelan, C.C. LaBranche.

Story Source:

Materials provided by DOE/Los Alamos National Laboratory. Note: Content may be edited for style and length.

Journal Reference:

1. B. Korber, W.M. Fischer, S. Gnanakaran, H. Yoon, J. Theiler, W. Abfalterer, N. Hengartner, E.E. Giorgi, T. Bhattacharya, B. Foley, K.M. Hastie, M.D. Parker, D.G. Partridge, C.M. Evans, T.M. Freeman, T.I. de Silva, C. McDanal, L.G. Perez, H. Tang, A. Moon-Walker, S.P. Whelan, C.C. LaBranche, E.O. Saphire, D.C. Montefiori, on behalf of theSheffield COVID-19 Genomics Group. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell, July 2, 2020; DOI: 10.1016/j.cell.2020.06.043

First childhood flu helps explain why virus hits some people harder than others

Taking temperature of child (stock image).

Why are some people better able to fight off the flu than others? Part of the answer, according to a new study, is related to the first flu strain we encounter in childhood.

Scientists from UCLA and the University of Arizona have found that people's ability to fight off the flu virus is determined not only by the subtypes of flu they have had throughout their lives, but also by the sequence in which they are been infected by the viruses. Their study is published in the open-access journal PLoS Pathogens.

The research offers an explanation for why some people fare much worse than others when infected with the same strain of the flu virus, and the findings could help inform strategies for minimizing the effects of the seasonal flu.

In addition, UCLA scientists, including Professor James Lloyd-Smith, who also was a senior author of the PLoS Pathogens research, recently completed a study that analyzes travel-related screening for the new novel coronavirus 2019-nCoV.

The researchers report that screening travelers is not very effective for the 2019 coronavirus -- that it will catch less than half of infected travelers, on average -- and that most infected travelers are undetectable, meaning that they have no symptoms yet, and are unaware that they have been exposed. So stopping the spread of the virus is not a matter of just enhancing screening methods at airports and other travel hubs.

"This puts the onus on government officials and public health officials to follow up with travelers after they arrive, to isolate them and trace their contacts if they get sick later," said Lloyd-Smith, a UCLA professor of ecology and evolutionary biology. Many governments have started to impose quarantines, or even travel bans, as they realize that screening is not sufficient to stop the spread of the coronavirus.

One major concern, Lloyd-Smith said, is that other countries, especially developing nations, lack the infrastructure and resources for those measures, and are therefore vulnerable to importing the disease.

"Much of the public health world is very concerned about the virus being introduced into Africa or India, where large populations exist do not have access to advanced medical care," he said.

The researchers, including scientists from the University of Chicago and the London School of Tropical Hygiene and Medicine, have developed a free online app where people can calculate the effectiveness of travel screening based on a range of parameters.

Solving a decades-old question

The PLoS Pathogens study may help solve a problem that had for decades vexed scientists and health care professionals: why the same strain of the flu virus affects people with various degrees of severity.

A team that included some of the same UCLA and Arizona scientists reported in 2016 that exposure to influenza viruses during childhood gives people partial protection for the rest of their lives against distantly related influenza viruses. Biologists call the idea that past exposure to the flu virus determines a person's future response to infections "immunological imprinting."

The 2016 research helped overturn a commonly held belief that previous exposure to a flu virus conferred little or no immunological protection against strains that can jump from animals into humans, such as those causing the strains known as swine flu or bird flu. Those strains, which have caused hundreds of spillover cases of severe illness and death in humans, are of global concern because they could gain mutations that allow them to readily jump not only from animal populations to humans, but also to spread rapidly from person to person.

In the new study, the researchers investigated whether immunological imprinting could explain people's response to flu strains already circulating in the human population and to what extent it could account for observed discrepancies in how severely the seasonal flu affects people in different age groups.

To track how different strains of the flu virus affect people at different ages, the team analyzed health records that the Arizona Department of Health Services obtains from hospitals and private physicians.

Two subtypes of influenza virus, H3N2 and H1N1, have been responsible for seasonal outbreaks of the flu over the past several decades. H3N2 causes the majority of severe cases in high-risk elderly people and the majority of deaths from the flu. H1N1 is more likely to affect young and middle-aged adults, and causes fewer deaths.

The health record data revealed a pattern: People first exposed to the less severe strain, H1N1, during childhood were less likely to end up hospitalized if they encountered H1N1 again later in life than people who were first exposed to H3N2. And people first exposed to H3N2 received extra protection against H3N2 later in life.

The researchers also analyzed the evolutionary relationships between the flu strains. H1N1 and H3N2, they learned, belong to two separate branches on the influenza "family tree," said James Lloyd-Smith, a UCLA professor of ecology and evolutionary biology and one of the study's senior authors. While infection with one does result in the immune system being better prepared to fight a future infection from the other, protection against future infections is much stronger when one is exposed to strains from the same group one has battled before, he said.

The records also revealed another pattern: People whose first childhood exposure was to H2N2, a close cousin of H1N1, did not have a protective advantage when they later encountered H1N1. That phenomenon was much more difficult to explain, because the two subtypes are in the same group, and the researchers' earlier work showed that exposure to one can, in some cases, grant considerable protection against the other.

"Our immune system often struggles to recognize and defend against closely related strains of seasonal flu, even though these are essentially the genetic sisters and brothers of strains that circulated just a few years ago," said lead author Katelyn Gostic, who was a UCLA doctoral student in Lloyd-Smith's laboratory when the study was conducted and is now a postdoctoral fellow at the University of Chicago. "This is perplexing because our research on bird flu shows that deep in our immune memory, we have some ability to recognize and defend against the distantly related, genetic third cousins of the strains we saw as children.

"We hope that by studying differences in immunity against bird flus -- where our immune system shows a natural ability to deploy broadly effective protection -- and against seasonal flus -- where our immune system seems to have bigger blind spots -- we can uncover clues useful to universal influenza vaccine development."

Around the world, influenza remains a major killer. The past two flu seasons have been more severe than expected, said Michael Worobey, a co-author of the study and head of the University of Arizona's department of ecology and evolutionary biology. In the 2017-18 season, 80,000 people died in the U.S., more than in the swine flu pandemic of 2009, he said.

People who had their first bout of flu as children in 1955 -- when the H1N1 was circulating but the H3N2 virus was not -- were much more likely to be hospitalized with an H3N2 infection than an H1N1 infection last year, when both strains were circulating, Worobey said.

"The second subtype you're exposed to is not able to create an immune response that is as protective and durable as the first," he said.

The researchers hope that their findings could help predict which age groups might be severely affected during future flu seasons based on the subtype circulating. That information could also help health officials prepare their response, including decisions about who should receive certain vaccines that are only available in limited quantities.

The research was funded by the National Institutes of Health, the National Science Foundation, DARPA and the David and Lucile Packard Foundation. In 2018, the NIH's National Institute of Allergy and Infectious Diseases announced a strategic plan to develop a universal flu vaccine.

The study's co-authors are Rebecca Bridge of the Arizona Department of Health Services and Cecile Viboud of the Fogarty International Center at the NIH.

---

Story Source:

Materials provided by University of California - Los Angeles. Original written by Stuart Wolpert and Daniel Stolte. Note: Content may be edited for style and length.

First childhood flu helps explain why virus hits some people harder than others

Taking temperature of child (stock image).

Why are some people better able to fight off the flu than others? Part of the answer, according to a new study, is related to the first flu strain we encounter in childhood.

Scientists from UCLA and the University of Arizona have found that people's ability to fight off the flu virus is determined not only by the subtypes of flu they have had throughout their lives, but also by the sequence in which they are been infected by the viruses. Their study is published in the open-access journal PLoS Pathogens.

The research offers an explanation for why some people fare much worse than others when infected with the same strain of the flu virus, and the findings could help inform strategies for minimizing the effects of the seasonal flu.

In addition, UCLA scientists, including Professor James Lloyd-Smith, who also was a senior author of the PLoS Pathogens research, recently completed a study that analyzes travel-related screening for the new novel coronavirus 2019-nCoV.

The researchers report that screening travelers is not very effective for the 2019 coronavirus -- that it will catch less than half of infected travelers, on average -- and that most infected travelers are undetectable, meaning that they have no symptoms yet, and are unaware that they have been exposed. So stopping the spread of the virus is not a matter of just enhancing screening methods at airports and other travel hubs.

"This puts the onus on government officials and public health officials to follow up with travelers after they arrive, to isolate them and trace their contacts if they get sick later," said Lloyd-Smith, a UCLA professor of ecology and evolutionary biology. Many governments have started to impose quarantines, or even travel bans, as they realize that screening is not sufficient to stop the spread of the coronavirus.

One major concern, Lloyd-Smith said, is that other countries, especially developing nations, lack the infrastructure and resources for those measures, and are therefore vulnerable to importing the disease.

"Much of the public health world is very concerned about the virus being introduced into Africa or India, where large populations exist do not have access to advanced medical care," he said.

The researchers, including scientists from the University of Chicago and the London School of Tropical Hygiene and Medicine, have developed a free online app where people can calculate the effectiveness of travel screening based on a range of parameters.

Solving a decades-old question

The PLoS Pathogens study may help solve a problem that had for decades vexed scientists and health care professionals: why the same strain of the flu virus affects people with various degrees of severity.

A team that included some of the same UCLA and Arizona scientists reported in 2016 that exposure to influenza viruses during childhood gives people partial protection for the rest of their lives against distantly related influenza viruses. Biologists call the idea that past exposure to the flu virus determines a person's future response to infections "immunological imprinting."

The 2016 research helped overturn a commonly held belief that previous exposure to a flu virus conferred little or no immunological protection against strains that can jump from animals into humans, such as those causing the strains known as swine flu or bird flu. Those strains, which have caused hundreds of spillover cases of severe illness and death in humans, are of global concern because they could gain mutations that allow them to readily jump not only from animal populations to humans, but also to spread rapidly from person to person.

In the new study, the researchers investigated whether immunological imprinting could explain people's response to flu strains already circulating in the human population and to what extent it could account for observed discrepancies in how severely the seasonal flu affects people in different age groups.

To track how different strains of the flu virus affect people at different ages, the team analyzed health records that the Arizona Department of Health Services obtains from hospitals and private physicians.

Two subtypes of influenza virus, H3N2 and H1N1, have been responsible for seasonal outbreaks of the flu over the past several decades. H3N2 causes the majority of severe cases in high-risk elderly people and the majority of deaths from the flu. H1N1 is more likely to affect young and middle-aged adults, and causes fewer deaths.

The health record data revealed a pattern: People first exposed to the less severe strain, H1N1, during childhood were less likely to end up hospitalized if they encountered H1N1 again later in life than people who were first exposed to H3N2. And people first exposed to H3N2 received extra protection against H3N2 later in life.

The researchers also analyzed the evolutionary relationships between the flu strains. H1N1 and H3N2, they learned, belong to two separate branches on the influenza "family tree," said James Lloyd-Smith, a UCLA professor of ecology and evolutionary biology and one of the study's senior authors. While infection with one does result in the immune system being better prepared to fight a future infection from the other, protection against future infections is much stronger when one is exposed to strains from the same group one has battled before, he said.

The records also revealed another pattern: People whose first childhood exposure was to H2N2, a close cousin of H1N1, did not have a protective advantage when they later encountered H1N1. That phenomenon was much more difficult to explain, because the two subtypes are in the same group, and the researchers' earlier work showed that exposure to one can, in some cases, grant considerable protection against the other.

"Our immune system often struggles to recognize and defend against closely related strains of seasonal flu, even though these are essentially the genetic sisters and brothers of strains that circulated just a few years ago," said lead author Katelyn Gostic, who was a UCLA doctoral student in Lloyd-Smith's laboratory when the study was conducted and is now a postdoctoral fellow at the University of Chicago. "This is perplexing because our research on bird flu shows that deep in our immune memory, we have some ability to recognize and defend against the distantly related, genetic third cousins of the strains we saw as children.

"We hope that by studying differences in immunity against bird flus -- where our immune system shows a natural ability to deploy broadly effective protection -- and against seasonal flus -- where our immune system seems to have bigger blind spots -- we can uncover clues useful to universal influenza vaccine development."

Around the world, influenza remains a major killer. The past two flu seasons have been more severe than expected, said Michael Worobey, a co-author of the study and head of the University of Arizona's department of ecology and evolutionary biology. In the 2017-18 season, 80,000 people died in the U.S., more than in the swine flu pandemic of 2009, he said.

People who had their first bout of flu as children in 1955 -- when the H1N1 was circulating but the H3N2 virus was not -- were much more likely to be hospitalized with an H3N2 infection than an H1N1 infection last year, when both strains were circulating, Worobey said.

"The second subtype you're exposed to is not able to create an immune response that is as protective and durable as the first," he said.

The researchers hope that their findings could help predict which age groups might be severely affected during future flu seasons based on the subtype circulating. That information could also help health officials prepare their response, including decisions about who should receive certain vaccines that are only available in limited quantities.

The research was funded by the National Institutes of Health, the National Science Foundation, DARPA and the David and Lucile Packard Foundation. In 2018, the NIH's National Institute of Allergy and Infectious Diseases announced a strategic plan to develop a universal flu vaccine.

The study's co-authors are Rebecca Bridge of the Arizona Department of Health Services and Cecile Viboud of the Fogarty International Center at the NIH.

---

Story Source:

Materials provided by University of California - Los Angeles. Original written by Stuart Wolpert and Daniel Stolte. Note: Content may be edited for style and length.

Mosquitoes engineered to repel dengue virus

Aedes aegypti mosquito (stock image).

An international team of scientists has synthetically engineered mosquitoes that halt the transmission of the dengue virus.

Led by biologists at the University of California San Diego, the research team describes details of the achievement in Aedes aegypti mosquitoes, the insects that spread dengue in humans, on January 16 in the journal PLOS Pathogens.

Researchers in UC San Diego Associate Professor Omar Akbari's lab worked with colleagues at Vanderbilt University Medical Center in identifying a broad spectrum human antibody for dengue suppression. The development marks the first engineered approach in mosquitoes that targets the four known types of dengue, improving upon previous designs that addressed single strains.

They then designed the antibody "cargo" to be synthetically expressed in female A. aegypti mosquitoes, which spread the dengue virus.

"Once the female mosquito takes in blood, the antibody is activated and expressed -- that's the trigger," said Akbari, of the Division of Biological Sciences and a member of the Tata Institute for Genetics and Society. "The antibody is able to hinder the replication of the virus and prevent its dissemination throughout the mosquito, which then prevents its transmission to humans. It's a powerful approach."

Akbari said the engineered mosquitoes could easily be paired with a dissemination system, such as a gene drive based on CRISPR/CAS-9 technology, capable of spreading the antibody throughout wild disease-transmitting mosquito populations.

"It is fascinating that we now can transfer genes from the human immune system to confer immunity to mosquitoes. This work opens up a whole new field of biotechnology possibilities to interrupt mosquito-borne diseases of man," said coauthor James Crowe, Jr., M.D., director of the Vanderbilt Vaccine Center at Vanderbilt University Medical Center in Nashville, Tenn.

According to the World Health Organization, dengue virus threatens millions of people in tropical and sub-tropical climates. Severe dengue is a leading cause of serious illness and death among children in many Asian and Latin American countries. The Pan American Health Organization recently reported the highest number of dengue cases ever recorded in the Americas. Infecting those with compromised immune systems, dengue victims suffer flu-like symptoms, including severe fevers and rashes. Serious cases can include life-threatening bleeding. Currently no specific treatment exists and thus prevention and control depend on measures that stop the spread of the virus.

"This development means that in the foreseeable future there may be viable genetic approaches to controlling dengue virus in the field, which could limit human suffering and mortality," said Akbari, whose lab is now in the early stages of testing methods to simultaneously neutralize mosquitoes against dengue and a suite of other viruses such as Zika, yellow fever and chikungunya.

"Mosquitoes have been given the bad rap of being the deadliest killers on the planet because they are the messengers that transmit diseases like malaria, dengue, chikungunya, Zika and yellow fever that collectively put 6.5 billion people at risk globally," said Suresh Subramani, professor emeritus of molecular biology at UC San Diego and global director of the Tata Institute for Genetics and Society (TIGS). "Until recently, the world has focused on shooting (killing) this messenger. Work from the Akbari lab and at TIGS is aimed at disarming the mosquito instead by preventing it from transmitting diseases, without killing the messenger. This paper shows that it is possible to immunize mosquitoes and prevent their ability to transmit dengue virus, and potentially other mosquito-borne pathogens."

Coauthors of the research include: UC San Diego graduate student Stephanie Gamez; Anna Buchman and Ming Li of the Section of Cell and Developmental Biology, Division of Biological Sciences, UC San Diego; Igor Antoshechkin of the California Institute of Technology, Shin-Hang Lee, Shin-Wei Wang and Chun-Hong Chen of the National Health Research Institutes (Taiwan); and Melissa Klein, Jean-Bernard Duchemin and Prasad Paradkar of CSIRO Health and Biosecurity.

---

Story Source:

Materials provided by University of California - San Diego. Original written by Mario Aguilera. Note: Content may be edited for style and length.

Mosquitoes engineered to repel dengue virus

Aedes aegypti mosquito (stock image).

An international team of scientists has synthetically engineered mosquitoes that halt the transmission of the dengue virus.

Led by biologists at the University of California San Diego, the research team describes details of the achievement in Aedes aegypti mosquitoes, the insects that spread dengue in humans, on January 16 in the journal PLOS Pathogens.

Researchers in UC San Diego Associate Professor Omar Akbari's lab worked with colleagues at Vanderbilt University Medical Center in identifying a broad spectrum human antibody for dengue suppression. The development marks the first engineered approach in mosquitoes that targets the four known types of dengue, improving upon previous designs that addressed single strains.

They then designed the antibody "cargo" to be synthetically expressed in female A. aegypti mosquitoes, which spread the dengue virus.

"Once the female mosquito takes in blood, the antibody is activated and expressed -- that's the trigger," said Akbari, of the Division of Biological Sciences and a member of the Tata Institute for Genetics and Society. "The antibody is able to hinder the replication of the virus and prevent its dissemination throughout the mosquito, which then prevents its transmission to humans. It's a powerful approach."

Akbari said the engineered mosquitoes could easily be paired with a dissemination system, such as a gene drive based on CRISPR/CAS-9 technology, capable of spreading the antibody throughout wild disease-transmitting mosquito populations.

"It is fascinating that we now can transfer genes from the human immune system to confer immunity to mosquitoes. This work opens up a whole new field of biotechnology possibilities to interrupt mosquito-borne diseases of man," said coauthor James Crowe, Jr., M.D., director of the Vanderbilt Vaccine Center at Vanderbilt University Medical Center in Nashville, Tenn.

According to the World Health Organization, dengue virus threatens millions of people in tropical and sub-tropical climates. Severe dengue is a leading cause of serious illness and death among children in many Asian and Latin American countries. The Pan American Health Organization recently reported the highest number of dengue cases ever recorded in the Americas. Infecting those with compromised immune systems, dengue victims suffer flu-like symptoms, including severe fevers and rashes. Serious cases can include life-threatening bleeding. Currently no specific treatment exists and thus prevention and control depend on measures that stop the spread of the virus.

"This development means that in the foreseeable future there may be viable genetic approaches to controlling dengue virus in the field, which could limit human suffering and mortality," said Akbari, whose lab is now in the early stages of testing methods to simultaneously neutralize mosquitoes against dengue and a suite of other viruses such as Zika, yellow fever and chikungunya.

"Mosquitoes have been given the bad rap of being the deadliest killers on the planet because they are the messengers that transmit diseases like malaria, dengue, chikungunya, Zika and yellow fever that collectively put 6.5 billion people at risk globally," said Suresh Subramani, professor emeritus of molecular biology at UC San Diego and global director of the Tata Institute for Genetics and Society (TIGS). "Until recently, the world has focused on shooting (killing) this messenger. Work from the Akbari lab and at TIGS is aimed at disarming the mosquito instead by preventing it from transmitting diseases, without killing the messenger. This paper shows that it is possible to immunize mosquitoes and prevent their ability to transmit dengue virus, and potentially other mosquito-borne pathogens."

Coauthors of the research include: UC San Diego graduate student Stephanie Gamez; Anna Buchman and Ming Li of the Section of Cell and Developmental Biology, Division of Biological Sciences, UC San Diego; Igor Antoshechkin of the California Institute of Technology, Shin-Hang Lee, Shin-Wei Wang and Chun-Hong Chen of the National Health Research Institutes (Taiwan); and Melissa Klein, Jean-Bernard Duchemin and Prasad Paradkar of CSIRO Health and Biosecurity.

---

Story Source:

Materials provided by University of California - San Diego. Original written by Mario Aguilera. Note: Content may be edited for style and length.

Breakthrough in Zika virus vaccine

Illustration of Zika virus in blood (stock image).

Credit: © Kateryna_Kon / Adobe Stock

Researchers from the University of Adelaide have made significant advances in developing a novel vaccine against Zika virus, which could potentially lead to global elimination of the disease.

The virology team, led by Professor Eric Gowans and Dr Branka Grubor-Bauk -- based at the Basil Hetzel Institute for Translational Health Research and supported by The Hospital Research Foundation -- has developed a vaccine that prevents Zika infection in pre-clinical models of the disease.

Their findings have been published today in the leading international journal Science Advances.

Zika is a mosquito-transmitted 'flavivirus' which can cause microcephaly (a birth defect where a baby's head is significantly smaller than expected) and severe birth defects in infants born to infected mothers.

The introduction of an effective vaccine for Zika will prevent infection of pregnant women and the resultant congenital effects in the unborn child.

Dr Grubor-Bauk, senior research officer with the Adelaide Medical School, said the team had developed a novel vaccine against Zika that proved effective in mouse models.

"This is the first vaccine study that shows that a T cell-based vaccine can confer protection against a systemic Zika infection,'' she said.

"Our vaccine offers an advantage over other vaccines in development by eliminating the ongoing concerns in the field about enhancement of infection following exposure to dengue virus. This finding demonstrates for the first time that protective T cell vaccines against Zika are achievable.

"Zika virus is extremely detrimental if you're pregnant and there has been no therapy or vaccine available to date. If we can progress this work and immunise women who are of reproductive age and most at risk, we can stop the devastating effects of Zika infection in pregnancy and make a huge difference to the health of the global community."

This research, which has been years in the making, has progressed to this significant stage thanks to funding from National Foundation for Medical Research and Innovation (NFMRI) and ongoing funding from The Hospital Research Foundation.

The work was done in collaboration with eminent global vaccine researcher Prof Dan Barouch, Director of Harvard Medical School's Centre for Virology and Vaccine Research (CVVR) at Beth Israel Deaconess Medical Centre; as well as Adelaide's Prof Sarah Robertson, Director of the Robinson Research Institute, University of Adelaide; and other scientists from the universities of Adelaide, South Australia and Flinders.

"The next steps are to advance the vaccine to being ready for Phase I human clinical trials. This involves further pre-clinical studies which are vitally important to identify the most effective dosing and demonstrate protection against Zika infection in different pre-clinical models of the disease," Dr Grubor-Bauk said.

"The goal is to de-risk and create an attractive technology with a strong IP position, for licensing or co-development with a commercial partner.

"We are grateful to The Hospital Research Foundation which has been instrumental in their support of our research over this time. We could not have reached this point without them."

The findings of this study will also greatly inform other research in the development of flavivirus vaccines by shifting the focus of vaccine development from viral envelope and antibody-based vaccines to T-cell based vaccines.

Story Source:

Materials provided by University of Adelaide. Original written by Elisa Black. Note: Content may be edited for style and length.

Breakthrough in Zika virus vaccine

Illustration of Zika virus in blood (stock image).

Researchers from the University of Adelaide have made significant advances in developing a novel vaccine against Zika virus, which could potentially lead to global elimination of the disease.

The virology team, led by Professor Eric Gowans and Dr Branka Grubor-Bauk -- based at the Basil Hetzel Institute for Translational Health Research and supported by The Hospital Research Foundation -- has developed a vaccine that prevents Zika infection in pre-clinical models of the disease.

Their findings have been published today in the leading international journal Science Advances.

Zika is a mosquito-transmitted 'flavivirus' which can cause microcephaly (a birth defect where a baby's head is significantly smaller than expected) and severe birth defects in infants born to infected mothers.

The introduction of an effective vaccine for Zika will prevent infection of pregnant women and the resultant congenital effects in the unborn child.

Dr Grubor-Bauk, senior research officer with the Adelaide Medical School, said the team had developed a novel vaccine against Zika that proved effective in mouse models.

"This is the first vaccine study that shows that a T cell-based vaccine can confer protection against a systemic Zika infection,'' she said.

"Our vaccine offers an advantage over other vaccines in development by eliminating the ongoing concerns in the field about enhancement of infection following exposure to dengue virus. This finding demonstrates for the first time that protective T cell vaccines against Zika are achievable.

"Zika virus is extremely detrimental if you're pregnant and there has been no therapy or vaccine available to date. If we can progress this work and immunise women who are of reproductive age and most at risk, we can stop the devastating effects of Zika infection in pregnancy and make a huge difference to the health of the global community."

This research, which has been years in the making, has progressed to this significant stage thanks to funding from National Foundation for Medical Research and Innovation (NFMRI) and ongoing funding from The Hospital Research Foundation.

The work was done in collaboration with eminent global vaccine researcher Prof Dan Barouch, Director of Harvard Medical School's Centre for Virology and Vaccine Research (CVVR) at Beth Israel Deaconess Medical Centre; as well as Adelaide's Prof Sarah Robertson, Director of the Robinson Research Institute, University of Adelaide; and other scientists from the universities of Adelaide, South Australia and Flinders.

"The next steps are to advance the vaccine to being ready for Phase I human clinical trials. This involves further pre-clinical studies which are vitally important to identify the most effective dosing and demonstrate protection against Zika infection in different pre-clinical models of the disease," Dr Grubor-Bauk said.

"The goal is to de-risk and create an attractive technology with a strong IP position, for licensing or co-development with a commercial partner.

"We are grateful to The Hospital Research Foundation which has been instrumental in their support of our research over this time. We could not have reached this point without them."

The findings of this study will also greatly inform other research in the development of flavivirus vaccines by shifting the focus of vaccine development from viral envelope and antibody-based vaccines to T-cell based vaccines.

MS linked to variant of common herpes virus

Researchers at Karolinska Institutet have developed a new method to separate between two different types of a common herpes virus (HHV-6) that has been linked to multiple sclerosis. By analyzing antibodies in the blood against the most divergent proteins of herpesvirus 6A and 6B, the researchers were able to show that MS-patients carry the herpesvirus 6A to a greater extent than healthy individuals. The findings, published in Frontiers in Immunology, point to a role for HHV-6A in the development of MS.

Multiple sclerosis, MS, is an autoimmune disease that affects the central nervous system. The cause of the disease is unclear, but one plausible explanation is a virus tricks the immune system to attack the body's own tissue. Human Herpesvirus 6 (HHV-6) has previously been associated with MS, but in those studies it wasn't possible to distinguish between 6A and 6B. Through virus isolation from ill individuals, researchers have been able to show that HHV-6B can cause mild conditions such as roseola in children, but it has been unclear if HHV-6A is the cause of any disease.

According to estimates, as many as 80 percent of all children are infected with the HHV-6 virus before 2 years of age, and many also carry protection in the form of antibodies against this particular virus for the rest of their lives. But since it hasn't been possible to tell the two variants apart post-infection, it has been difficult to say whether HHV-6A or B is a risk factor for MS.

In this study, however, the researchers were able to distinguish between the A and B virus by analyzing antibodies in the blood against the proteins -- immediate early protein 1A and 1B (IE1A and IE1B) -- that diverge the most between the two viruses.

"This is a big breakthrough for both the MS and herpes virus research," says Anna Fogdell-Hahn, associate professor at the Department of Clinical Neuroscience at Karolinska Institutet and one of the study's senior authors. "For one, it supports the theory that HHV-6A could be a contributing factor to the development of MS. On top of that, we are now able, with this new method, to find out how common these two different types of HHV-6 are, something we haven't been able to do previously."

The researchers compared antibody levels in blood samples of some 8,700 MS-patients against more than 7,200 healthy people whose gender, date of birth, date of blood sample and other factors matched those with MS. They concluded that people with MS had a 55 percent higher risk of carrying antibodies against the HHV-6A protein than the control group. In a sub-group of almost 500 people, whose blood samples were drawn before the onset of the disease, the risk of developing MS in the future was more than doubled if they had a 6A viral infection. The younger the people were when the virus was first discovered in the blood, the higher the risk was of developing MS in the future. HHV-6B, on the other hand, was not positively associated with MS. Instead MS-patients had lower levels of antibodies toward IE1B than those without MS.

Antibodies toward Epstein-Barr virus (EBV), another herpes virus that is also associated with MS, were analyzed with the same method and the researchers were able to show that individuals affected with both viruses had an even greater risk of MS. This indicates that several virus infections could be acting jointly to increase the risk of MS.

"Both HHV-6A and 6B can infect our braincells, but they do it in slightly different ways. Therefore, it is now interesting to go forward and attempt to map out exactly how the viruses could affect the onset of MS," says Anna Fogdell-Hahn.

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Materials provided by Karolinska Institutet. Note: Content may be edited for style and length.

Ketogenic diet helps tame flu virus

Influenza virus illustration (stock image).

A high-fat, low-carbohydrate diet like the Keto regimen has its fans, but influenza apparently isn't one of them.

Mice fed a ketogenic diet were better able to combat the flu virus than mice fed food high in carbohydrates, according to a new Yale University study published Nov. 15 in the journal Science Immunology.

The ketogenic diet -- which for people includes meat, fish, poultry, and non-starchy vegetables -- activates a subset of T cells in the lungs not previously associated with the immune system's response to influenza, enhancing mucus production from airway cells that can effectively trap the virus, the researchers report.

"This was a totally unexpected finding," said co-senior author Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellular and Developmental Biology, and an investigator of the Howard Hughes Medical Institute.

The research project was the brainchild of two trainees -- one working in Iwasaki's lab and the other with co-senior author Visha Deep Dixit, the Waldemar Von Zedtwitz Professor of Comparative Medicine and of Immunobiology. Ryan Molony worked in Iwasaki's lab, which had found that immune system activators called inflammasomes can cause harmful immune system responses in their host. Emily Goldberg worked in Dixit's lab, which had shown that the ketogenic diet blocked formation of inflammasomes.

The two wondered if diet could affect immune system response to pathogens such as the flu virus.

They showed that mice fed a ketogenic diet and infected with the influenza virus had a higher survival rate than mice on a high-carb normal diet. Specifically, the researchers found that the ketogenic diet triggered the release of gamma delta T cells, immune system cells that produce mucus in the cell linings of the lung -- while the high-carbohydrate diet did not.

When mice were bred without the gene that codes for gamma delta T cells, the ketogenic diet provided no protection against the influenza virus.

"This study shows that the way the body burns fat to produce ketone bodies from the food we eat can fuel the immune system to fight flu infection," Dixit said.

Insulin can increase mosquitoes' immunity to West Nile virus

Mosquito

A discovery by a Washington State University-led research team has the potential to inhibit the spread of West Nile virus as well as Zika and dengue viruses.

In a study published today in the journal Cell Reports, researchers demonstrated that mammalian insulin activated an antiviral immunity pathway in mosquitoes, increasing the insects' ability to suppress the viruses.

Mosquito bites are the most common way humans are infected with flaviviruses, a virus family that includes West Nile, dengue and Zika. In humans, both West Nile and dengue can result in severe illness, even death. Zika has been linked to birth defects when pregnant women are infected.

"It's really important that we have some sort of protection against these diseases because currently, we don't have any treatments. If we're able to stop the infection at the level of the mosquito, then humans wouldn't get the virus," said Laura Ahlers, the study's lead author and a recent Ph.D. graduate from WSU. Ahlers is now a post-doctoral fellow with the National Institutes of Health in Bethesda, Maryland.

Working first with fruit flies, which have similar immune responses to mosquitoes, Ahlers and her colleagues identified an insulin-like receptor in the insects that, when activated, inhibits the replication of the West Nile virus in the flies. The researchers then elicited this same response in mosquitoes by feeding them blood containing elevated insulin. Subsequent tests showed activating this receptor was also effective in suppressing dengue and Zika in insect cells.

While it was already known that insulin boosts immune responses in mosquitoes, this is the first time insulin's connection to a particular immune response pathway, called JAK/STAT, has been identified. It is a significant step toward the long-term goal of creating an intervention, said Alan Goodman, WSU assistant professor and the corresponding author on the paper.

"If we can activate this arm of immunity through the insulin receptor in the mosquito, we can reduce the overall viral load in the mosquito population," Goodman said. "If the mosquitoes are carrying less virus when they bite you, they will transmit less of the virus, and there's a better chance you won't acquire the disease."

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Materials provided by Washington State University. Original written by Sara Zaske. Note: Content may be edited for style and length.