Daily Archives: July 17, 2020

As the world endures the impacts of a rapidly changing climatesea level rise, extreme weather events, warming and acidifying oceans (among many others)policy makers and the public should critically examine how food production contributes to these worrying trends. Animal agriculture may be the best place to start since, many scientists argue, its the single biggest cause of biodiversity loss and a significant source of greenhouse gas emissions.

Over a quarter of the worlds land surface is currently dedicated to raising animals for food, but that practice can be exceptionally wasteful. Despite taking up almost 80 percent of global agricultural land, livestock represents less than 20 percent of the worlds calories. Proper stewardship of the land, which absorbs nearly one-third of global greenhouse gas emissions, is critical in our fight against climate change, but human activities degrade roughly a quarter of it, and livestock production is perhaps the primary culprit.

To help combat these growing environmental challenges, concerned citizens around the world are eating more sustainable and arguably healthier diets that partially or entirely replace meat with fish, crustaceans, and other aquatic animals. Fish production generally has a lower environmental impact than land animal farming, owing to the fact that fish require less feed. Most fish are poikilotherms, which means they dont use energy to heat their bodies. And unlike most land animals (homeotherms), fish dont need to constantly maintain their body temperatures, which tend to fluctuate with their external environment. Moreover, the density of water carries the weight of the fish, eliminating the requirement for heavy bones.

Despite its lower environmental footprint, global fish productionwhich includes wild capture and aquaculture (fish farming)has its own sustainability issues. Around one-third of the worlds marine fish stocks have reached unsustainable levels due to overfishing. Simultaneously, the global demand for fish and nutritional oils containing omega-3 fatty acids is increasing rapidly as more consumers recognize that consuming them is linked to reduced cardiovascular disease risk. Saturation in capture fishing since the early 1990s means aquaculture is filling consumer demand for fish. But without significant changes, aquaculture isnt a long-term solution.

Fortunately, a valuable but misunderstood tool can help the industry become more sustainable. Of course, Im talking about biotechnology. Genetic engineering has sped up the production of fish, and enabled the development of sustainable fish feed sources and nutritional oils. All three innovations are marching toward commercialization, and the evidence indicates their collective impact will be enormous.

While commercial fish farms have greatly improved their production systems over the years, feeding fish with fish (primarily fishmeal and oils) still poses a significant sustainability threat. In 2018, global fish production reached around 179 million tons, and humans ate about 88 percent of the produce (156 million tons) while about 10 percent (18 million tons) went towards producing fishmeal and fish oils. Finding alternative feed sources would slash the environmental footprint of aquaculture and contribute to global food security goals.

Breeding better fish

Fish maturity is based on physical features such as shape and size. The faster fish grow, the lower their environmental impact, so innovators have targeted faster growth rates as a solution to the industrys sustainability problem. In 2015, the Food and Drug Administration (FDA) approved a bioengineered Atlantic salmon for consumption after decades of rigorous scientific review. The FDA concluded that the genetically engineered AquAdvantage salmon is as safe to eat as any non-genetically engineered Atlantic, and also as nutritious. This salmon is approved for sale in Canada and is slated for commercialization in the US.

Scientists at the biotech firm AquaBounty introduced two different bits of genetic information from other fish species into a bioengineered salmon: a growth hormone gene from the fast-growing Chinook salmon controlled by a DNA switch (promoter) from the ocean pout. Because the Chinook growth hormone gene works overtime, AquaBountys salmon grows to full size in about half the time required by conventional salmonand consumes 25 percent less feed as a result.

Faster growth means the energy and carbon emissions required to produce the fish are lower. And since AquaBountys land-based aquaculture facilities are located in Canada and the US, transporting these fish to market generates lower carbon emission than delivering conventional salmon by air or ship. Additionally, the expansion of genetically engineered fish production could significantly reduce overfishing, since some of salmon feed comes from other wild fish.

Some environmentalists have voiced concerns about the consequences of bioengineered fish escaping into the wild. In theory, genetically engineered fish may flee to the wild, breed with their wild relatives and create a hybrid that could out-compete other fish in the marine ecosystem. Quite rightly, these are serious concerns that require proper attention and strong mitigation plans.

Considering the trade-off between hypothetical risks and the demonstrated benefits of biotechnology in fish production helps us evaluate the situation. AquAdvantage salmon are produced in land-based facilities and are sterile. Regulators at the FDA have therefore concluded its extremely unlikely that the fish could escape and establish themselves in the wild.

Shorter production time and lower feed and energy requirements clearly outweigh the low risk of fish escaping into the wild. And we get all these without compromising the nutritional value of the fish itself. AquaBounty is scheduled to begin producing its bioengineered salmon in the US before the end of 2020, making it the first genetically engineered food animal to hit US markets. As COVID-19 continues to put pressure on food supplies, the introduction of genetically engineered salmon helps illustrate how biotechnology can help solve critical problems.

Alternative fish feeds and fish oils

Bioengineered fish is an important step in the right direction, but it doesnt fully address aquacultures sustainability issues. The industry has developed non-fish based feeds, cutting use of fishmeal and fish oil from 30 million tons in 1994 to about 18 million tons in 2018. But there are concerns that fish products grown on alternative feeds arent providing the same nutritional value as those fed real fish, which is high in omega-3 oils. To understand why, we need to look at the chemistry of these fatty acids.

Omega-3 oils are long-chain polyunsaturated fatty acids existing mainly in three types: -linolenic acid (ALA); eicosapentaenoic acid (EPA); and docosahexaenoic acid (DHA). Plant oils contain ALA, which is the shorter version of EPA and DHA omega-3 fatty acids, typically found in marine organisms like microalgae and phytoplankton.

Our bodies cant make omega-3, so we mostly get it from eating fish, which incidentally also cant make omega-3 but accumulate it by eating microalgae and phytoplankton. As vegetable oils replace fish oil in aquafeeds, the level of beneficial fatty acids, EPA and DHA, have also declined considerably, reducing the nutritional value that fish offer. Therefore, the aquaculture industry needs to identify aquafeeds that are derived from alternative sources and provide the same level of nutrition.

Algae are a promising source to replace fish oil, but extracting algal oil is more expensive than producing fish oil and fishmeal, though the extraction technology is rapidly developing. Additionally, algae cultivation for aquafeed is sometimes limited to species that only produce DHA fatty acids, which means the algae-fed fish lack EPA, compromising their final nutritional value.

Again, scientists have turned to biotechnology to address this problem. Research teams have engineered plants like camelina and canola that contain high levels of EPA and DHA in their seed oil. These plants naturally produce the shorter version of omega-3, ALA, and scientists introduced microalgal genes that convert ALA into EPA and DHA omega-3 fatty acids typically found in fish. Research shows that fish fed with seed oil from these camelina plants show good growth, maintain feed efficiency and dont lose nutritional valueindicating that genetically engineered plants can provide a sustainable substitute for fish oil feeds.

Now innovators are aiming to produce omega-3 oils from camelina for aquafeeds and nutritional supplements. Biotech startup Yield10 Bioscience has fused artificial intelligence with synthetic biology to create a technology that identifies trait targets to produce better plants. Using their technology platform and genome editing, they have generated camelina plants that produce double seed yields with a high content of both EPA and DHA omega-3 oils. The company has recently launched field trials of their genome-edited seeds. They are scaling seed production, aiming to plant thousands of acres of camelina to produce plant-based omega-3 oil products for fish feed and human nutrition soon. Crucially, the USDA announced in January 2020 that it wont regulate gene-edited camelina, accelerating development of this sustainable omega-3 oil source.

Biotechnology is already accelerating production of environmentally friendly salmon, and is poised to provide more sustainable fish feed and nutritional oils in the coming years. It could also bring aquaculture production costs down, reducing incentives to overfish our oceans, which will no doubt be better for the marine ecosystem.

Surging fish demand will only be met by sustainable, low-cost solutions, enabled in key instances by biotechnology. Technical details aside, the benefits of broader biotechnology adoption in aquaculture will extend beyond the developed world to improve the lives of those most in needimpoverished people in the developing world.

Rupesh Paudyal holds a PhD in plant science and covers agriculture and the environment as a freelance writer. Visit his website and follow him on Twitter @TalkPlant

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Viewpoint: Fish farming has a sustainability problem and genetic engineering might be the solution - Genetic Literacy Project

DAVIS, Calif.--(BUSINESS WIRE)--BioConsortia, Inc., innovator of microbial solutions in crop protection, soil fertility, and yield improvement, welcomes Dr. Damian Curtis to the company as Director of Synthetic Biology and Genomics. He will lead new technology development in strain improvement and engineering for BioConsortias next generation of biopesticides, biostimulants and nitrogen fixation products.

Damian has 15 years of industrial experience with Bayer, AgraQuest and Exelixis. He is a recognized technology leader in genetic engineering and most recently he managed the microbial genetics functions in Biologics R&D at Bayer CropScience, where he also supported global projects including the Poncho/VOTiVO 2.0 product.

Damian holds a PhD in molecular biology & biochemistry from Oregon Health and Sciences University and a BS in molecular biology & chemistry from San Jose State University.

Damian is an exceptional leader in technology innovation and is well recognized for his talent in microbial genetics and engineering in the Ag biological space, said Hong Zhu, SVP Research & Development for BioConsortia. I am very pleased to have him join our R&D leadership team, especially as we are entering a new, exciting phase of growth and technology expansion to solve tough agricultural problems such as nitrogen overuse and to bring more high-performance biologicals to our partners and growers.

With a pipeline of highly effective conventional microbial fungicides, nematicides and biostimulants moving into the registration phase, BioConsortia is turning its focus to advance the next generation of products from their synthetic biology program.

As leader of the in-house Gene Editing and Synthetic Biology Platform, Damian will improve the genetics of BioConsortias already robust, spore-forming microbial leads in order to enhance performance of the naturally occurring nitrogen fixation bacteria. In addition to the development of new nitrogen fixation solutions, the team will also develop next generation biostimulants, fungicides, insecticides, and nematicides.

Damian Curtis said, I was first attracted to BioConsortia by their unique microbial discovery platform, and as I dug deeper into their library, leads, and products, as well as their current work on gene editing, I became more excited by the potential. I look forward to helping deliver products that will substantially change the industry.

Weve built a pipeline of highly effective natural products, and moved a number of effective biopesticide and biostimulant solutions into the registration phase, said Marcus Meadows-Smith, CEO. We are now implementing a program for next generation products. With Damians leadership we will magnify the natural capabilities of our nitrogen fixing microbes and deliver solutions that can replace the growers reliance on synthetic products, thereby opening up the $200 Billion fertilizer market for transformation.

About BioConsortia

BioConsortia, Inc. is developing effective microbial solutions that enhance plant phenotypes and increase crop yields. We are pioneering the use of directed selection in identifying teams of microbes - working like plant breeders and selecting plants based on targeted characteristics, then isolating the associated microbial community. Our proprietary Advanced Microbial Selection (AMS) process enriches the crop microbiome, allowing us to identify organisms that influence the expression of beneficial traits in plants. We are focused on developing products with superior efficacy, higher consistency, and breakthrough technologies in 3 key areas:1) Biopesticides: a pipeline of several biofungicides and nematicides with superior efficacy2) Biostimulants: growth promoting products that further increase yields in standard, high-yielding as well as stressed, agronomic conditions3) Nitrogen-fixation and fertilizer use efficiency: developing products for major non-legume row crops (such as corn and wheat)Our products are foliar, drench, seed treatment, in-furrow and granule products for a wide range of crops.

For inquiries and further information, please contact info@bioconsortia.com

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BioConsortia Welcomes Dr. Damian Curtis to Lead New Gene Editing and Synthetic Biology Platform for Next Generation Biopesticides, Biostimulants and...

The research report on Genetic Engineering Industry market provides a granular analysis of this industry vertical wherein notable market activities are thoroughly researched. Various market segmentations based on product type, application spectrum, and regional terrain are surveyed in-depth, while estimated share held by each segment by the end of forecast period is encompassed in the report.

The report also highlights the current remuneration of the market and offers an insight regarding the growth rate attained over the analysis timeframe. Vital parameters which will influence the market growth positively as well as negatively are enlisted. Further, the impact of COVID-19 pandemic outbreak on Genetic Engineering Industry market is also documented in the report.

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Major Points Covered in TOC:

Overview:Along with a broad overview of the global Genetic Engineering Industry market, this section gives an overview of the report to give an idea about the nature and contents of the research study.

Analysis of Strategies of Leading Players:Market players can use this analysis to gain a competitive advantage over their competitors in the Genetic Engineering Industry market.

Study on Key Market Trends:This section of the report offers a deeper analysis of the latest and future trends of the market.

Market Forecasts:Buyers of the report will have access to accurate and validated estimates of the total market size in terms of value and volume. The report also provides consumption, production, sales, and other forecasts for the Genetic Engineering Industry market.

Regional Growth Analysis:All major regions and countries have been covered in the report. The regional analysis will help market players to tap into unexplored regional markets, prepare specific strategies for target regions, and compare the growth of all regional markets.

Segmental Analysis:The report provides accurate and reliable forecasts of the market share of important segments of the Genetic Engineering Industry market. Market participants can use this analysis to make strategic investments in key growth pockets of the market.

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Genetic Engineering Industry Market Research Growth by Manufacturers, Regions, Type and Application, Forecast Analysis to 2025 - CueReport

In brief

COVID-19 vaccines are being developed with a previously unimaginable urgency. More groups are working faster than ever before to develop shots that will protect us from the novel coronavirus, and hopefully bring an end to the pandemic. At first glance, the more than 160 vaccine programs seem remarkably similar, mostly focused on inducing immunity to the coronavirus spike protein. A closer look reveals many differences, including the types of vaccine technologies deployed, how the spike protein is modified and displayed to our immune systems, and the kinds of immune responses these different approaches will elicit.

There was a moment, just over 200 days ago, when wed never heard of a coronavirus, when everything we did wasnt shrouded with the specter of COVID-19. We crammed into living rooms, sang, danced, clinked glasses, showed 2019 out the door. We eagerly welcomed the new decade, filled calendars, and planned trips. Hugs and handshakes werent a health threat. Walking past someone in a crowded grocery store wasnt anxiety inducing. Pictures of crowded beaches and bars didnt evoke anger. How the world has changed.

In early January, no one could have known how truly catastrophic this novel coronavirus would be. Yet before this particular virus, SARS-CoV-2, was discovered, a few prescient people had already begun preparing for it. For decades, virologists have warned of an impending pandemic. Were overdue, they said. Some groups even had the foresight to begin developing vaccines for a different coronavirus. Once SARS-CoV-2 emerged, those groups had a template to begin making vaccines for the yet-to-be-named disease, COVID-19.

As the pandemic grew, other companies and academic teams started working on their own vaccines for COVID-19. By early April, more than 100 programs were reportedly underway. Even then, vaccines remained a distant prospect. Amid shutdowns and social distancing, we simply yearned for summer, for a break from the virus. The reprieve never came.

Vaccines, for all intents and purposes, were the backup plan. Now, we need them more than ever.

Without a vaccine, I dont think we can put a lid on this, says Paul Young, a virologist developing a COVID-19 vaccine at the University of Queensland. It will continue to be a fire that rages through the world for quite some time until literally everyone is infected unless we are able to intervene.

For nearly 7 long months, SARS-CoV-2 has pushed us to our limits. By mid-July, the virus had infected more than 13 million people and killed more than 580,000. About a quarter of those recorded cases and deaths belong to the US, a fraction likely to rise as so many Americans seemingly give up on the simple public health precautions that other countries have used to curtail the spread of the virus.

Yet there is cause for hope. In those same 7 short months, scientists have made strides that might normally take 7 years. Companies are beginning large trials with tens of thousands of people this month to see if their experimental vaccines can prevent disease. The pandemic has spurred the fastest vaccine development programs in history. While some groups are pushing to have vaccines available this winter, maybe sooner, others think such timelines are preposterous, and potentially reckless. Many questions remain, but there are two things that nearly everyone can agree on.

First, we need a vaccine to end this pandemic. There is no doubt, says Daria Hazuda, vice president of infectious diseases discovery at Merck Research Laboratories. Given how widespread this is globally I just dont think it is going to go away by itself. Second, scientists are confident that at least one vaccine, and hopefully more, will eventually work. There is every reason to believe that we can make a vaccine against this kind of virus, says Paul Offit, a pediatrician and director of the Vaccine Education Center at Childrens Hospital of Philadelphia. I think it is very likely that we will have an effective vaccine by the middle of next year, he adds.

From that consensus, however, opinions diverge.

On the surface, all COVID-19 vaccine candidates have the same goal: generate an immune response that protects you from the virus. But under the hood, these vaccines use a range of technologiesfrom tried and true to new and untestedto teach our bodies how to defend itself against the virus.

This summer, C&EN interviewed more than three dozen scientists, doctors, and business leaders to illuminate the complementary, and occasionally conflicting, strategies employed by groups developing the most advanced and well-funded COVID-19 vaccines. Theres much to learn still, and more definitive answers will come in time, but we already know the questions we need to be asking to make an effective vaccine.

Heres how we get back to normal.

I. How hard is it to make a vaccine against a virus?

Scientists have devised many ways to protect against an infection. In mid-July, the World Health Organization had counted 23 COVID-19 vaccine programs in clinical testing, and another 140 in preclinical development. This is just an unprecedented effort, every possible vaccine strategy is being used, including ones that have never been used before, Offit says.

The most traditional approach to making a vaccine is to simply use the virus itself, allowing your immune cells to learn how to fight it without you actually having to suffer through the disease. Viruses can either be left alive but attenuatedwhere scientists take all the chutzpah out of itor they can be killed with chemicals and heat that leave them unable to replicate. Historically, some of the most effective vaccines, such as those for measles, polio, and smallpox are attenuated or inactivated vaccines.

Credit: Andrew Caballero-Reynolds/AFP via Getty Images

A vial with an experimental COVID-19, vaccine at Novavax ln Gaithersburg, Maryland

Today, the most popular approaches for making new vaccines all focus on isolating the specific part of the virus believed to be most important for immunity. For SARS-CoV-2, that part is incontrovertibly the spike proteinimmediately recognizable in cartoons of the virus as the mushroom-like knobs studding its spherical surface. The coronavirus uses these spike proteins to grab hold of a human protein called ACE2, the first step in an infection. Nearly every COVID-19 vaccine candidate shares the objective of trying to prevent this interaction between the spike protein and ACE2.

Giving our immune cells target practice with a harmless form of the spike protein should allow them to halt the real virus in its tracks. A large number of groups are working on making the spike protein itself, detached from the virus, as the primary vaccine ingredient. Genetic engineering allows scientists to easily copy and paste the genetic code of the spike protein into cells that are optimized to grow in large vats, where they crank out large quantities of the protein. Vaccines for hepatitis B, shingles, and other diseases are made with this approach, which yields whats known as a subunit protein vaccine.

But developing manufacturing processes for any of these more traditional vaccines typically takes months, if not much longer. Making attenuated or inactivated vaccines requires special facilities with extra safety precautions to grow large numbers of the actual virus, while subunit protein vaccines require scientists to optimize cells that can make the viral protein and then patiently wait for the cells to multiply.

Recently, theres been growing excitement for experimental vaccines that take a different and faster route. Based on newer technologies, these vaccines simply contain the genetic code for the spike protein, and come in several forms, including DNA, messenger RNA, and viral vectorswhere a harmless virus is rejiggered into a gene-delivery vessel. But the end goal for all of them is the same: transport the genetic instructions for the spike protein into human cells in order to temporarily turn those cells into spike protein factories. No DNA or mRNA vaccines have ever received regulatory approval, and only two viral vector vaccinesboth to prevent Ebola virushave been licensed for humans.

Without a vaccine, I dont think we can put a lid on this, It will continue to be a fire that rages through the world for quite some time until literally everyone is infected unless we are able to intervene.

Paul Young, virologist, University of Queensland

Frank DeRosa, the chief technology officer of the mRNA company Translate Bio, explains that mRNA vaccines let our own cells make the spike protein just like they would if we were infected with the real virus. These vaccines, along with DNA and viral vector vaccines, allow the spike protein to be trafficked to the cell membrane surface where it is displayed, or else chopped up and presented in pieces to immune cells. You are just letting the body do what it would do normally, DeRosa says. Thats one of the advantages of mRNA.

Gene-based vaccines should also allow the protein to undergo glycosylation, a cellular process of tacking sugars onto the protein in specific patterns, which will give the immune system a more accurate mug shot of the spike protein. These sugar patterns can differ in subunit proteins, depending on the kinds of cells used to manufacture them.

Genetic vaccines have another key advantage: they are breathtakingly fast to design and produce. The only thing that changes significantly between two genetic vaccines is the segment of code being delivered. The manufacturing process for one RNA is a lot like the manufacturing process for another RNA, says Phil Dormitzer, Pfizers chief scientific officer for viral vaccines. The same is largely true for DNA vaccines, and true to a lesser degree for viral vector vaccines. Its why most of the fastest moving programs for COVID-19 are gene-based vaccines.

The current record speed for making a modern vaccine is Mercks viral vector vaccine for Ebola, which took 5 years to design, test, and earn government approval. For COVID-19, many companies say that process could be collapsed into a year or two. Some firms, including AstraZeneca, Moderna, and Pfizer, expect to have efficacy data this fall, and the US government plans to preorder 300 million doses ready for distribution by January 2021.

Those timelines have plenty of skeptics. The notion that we can have something done by the fall is frankly ludicrous, that is just not going to happen, says Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development. I would suspect that by this time next year we are still going to be looking forward to when that first vaccine hits the market.

More than 160 vaccines are in the works to prevent COVID-19. Here are the major types of technologies being used to make them.

Attenuated and inactivated virus vaccines

Attenuated virus vaccines contain a living but weakened version of SARS-CoV-2. Inactivated virus vaccines contain SARS-CoV-2 that has been killed with heat or chemicals like -propiolactone or formalin. Several childhood vaccines are attenuated or inactivated virus vaccines.

Subunit protein vaccines

Subunit protein vaccines contain the SARS-CoV-2 spike protein, which the virus uses to enter human cells. These vaccines often include adjuvants, which are molecules that stimulate the innate immune system to help simulate a natural infection. More groups are developing subunit protein vaccines for COVID-19 than any other technology.

Viral vector vaccines

Viral vector vaccines use a different virussuch as the adenovirus, measles virus, or vesicular stomatitis virusthat is genetically engineered to carry the gene for the SARS-CoV-2 spike protein, which will be made by our cells. Viral vector vaccines for preventing Ebola have recently been approved, but others are still experimental.

Nucleic acid vaccines

Nucleic acid vaccines encode genetic instructions for the SARS-CoV-2 spike protein into DNA, delivered into our cells with an electric shock, or RNA, delivered into our cells via a lipid nanoparticle. These vaccines can be rapidly designed and manufactured, but no DNA or RNA vaccine has been approved for humans.

II. Does the immune system view all vaccines equally?

Most vaccine developers believe that the potential protection offered by these vaccines hinges on teaching our immune cells to make the right kind of antibodies. In theory, antibodies can bind to any part of the spike protein, but only certain ones, the so-called neutralizing antibodies, bind to the spike protein in a manner that prevents the virus from infecting our cells.

Neutralizing antibodies are the most important biomarker to follow in the vaccine studies, and higher the antibody titers, the better, says John Shiver, senior vice president for global vaccines R&D at Sanofi.

You might imagine that the best way to get those high levels of neutralizing antibodies is to simply present the spike protein in its most natural form. But the spike protein is a wily shapeshifter, and many groups think that tweaking the spike protein will be necessary to induce a good neutralizing antibody response.

After the spike protein binds to ACE2, it undergoes a dramatic transformation. A spring-loaded portion of the spike shoots into the human cell membrane and then pulls the virus and cell so close together that their membranes fuse. This allows the virus to spill its genes and guts into the cell, where it begins replicating.

So scientists think there are probably two major ways an antibody can prevent infection: it can either directly block the spikes interaction with ACE2 in the first place, or it can gum up the spikes spring-loaded machinery and impede its fusion with our cells.

In 2016, while scientists were studying the spike protein of a different coronavirus, they discovered that embedding two prolinesthe most rigid of amino acidsin a particular part of the spike helped lock it into the shape that it takes before binding ACE2. Many researchers believe it is crucial to show your immune cells this so-called prefusion form of the spike protein in order to make antibodies that prevent infection. In contrast, if the vaccine teaches the immune system to make antibodies to the postfusion form, the shape the spike protein takes after binding to a cell, those antibodies will bind to the spike too late to prevent infection, says Andrew Ward, a structural biologist at Scripps Research who co-led the study.

Before the pandemic, that double proline mutation, called the 2P mutation, proved generalizable to several coronavirus spike proteins. So when SARS-CoV-2 emerged in early January, researchers were able to quickly add this mutation into the design of a COVID-19 vaccine. The mRNA company Moderna and researchers at the National Institute of Allergy and Infectious Diseases (NIAID) made a somewhat risky decision to begin manufacturing a COVID-19 vaccine based on the viruss spike sequence and the addition of the 2P mutation without any further experiments, explains Barney Graham, deputy director of the Vaccine Research Center at NIAID.

Since then the 2P mutation has made its way into subunit protein vaccines, mRNA vaccines, and viral vector vaccines. Jason McLellan, the scientist who discovered the 2P mutation, is now looking for other promising ones. His lab at the University of Texas at Austin has tested more than 100 additional mutations, which led to the creation of a novel prefusion spike protein dubbed HexaPro. Its more stable, and, when plugged into an mRNA vaccine, causes cells to make 10 times the amount of spike protein. He says companies making COVID-19 vaccines are already testing HexaPro in lab studies, and his lab is working on further improvement. We are always tweaking, he says. You can kind of do this forever but at some point you just have to pick something and move it forward.

Credit: Jason McLellan

The HexaPro spike protein, invented by Jason McLellans lab at the University of Texas at Austin, contains 6 proline mutations (red and blue spheres) that help stabilize the SARS-CoV-2 spike protein in its prefusion structure. The S1 subunit (transparent white) contacts the human cell and the S2 subunit (colored ribbons) contains the spring-loaded machinery that helps the virus fuse with the cell.

Other groups are making their own unique modifications to the prefusion spike. Scientists at the University of Queensland have made a subunit protein vaccine where the trimer of the spike is held together by what Queensland virologist Keith Chappell calls a molecular clamp. It is gripped at the base, and the top has natural flexibility, he says.

Other groups are forgoing the prefusion conformation in favor of a more natural, functional spike protein. That includes the DNA vaccine company Inovio Pharmaceuticals, which used this approach to elicit neutralizing antibodies in people who got its experimental MERS vaccine.

One of Mercks two viral vector vaccines is based on vesicular stomatitis virus (VSV), also used to make the firms recently licensed Ebola vaccine, Ervebo. Unlike the adenoviral vector vaccines under development for COVID-19, which just carry the genetic instructions for the spike protein, the VSV viral vector is designed to display the SARS-CoV-2 spike protein on its surface, where it can be used to enter human cells. It is kind of an authentic presentation, says Christopher Parks, whose lab led the design of the vaccine at IAVI, before Merck said it would test it in humans.

We can make effective vaccines quite quickly. But safety is not something that can be measured in a single time point. It has to be observed over a period of time.

David Dowling, vaccine researcher, BostonChildrens Hospital

Another strategy is to use just a key fragment of the spike protein. It turns out that the most potent neutralizing antibodies made by people who recover from COVID-19 almost always target a particular part of the spike protein. That key section, called the receptor-binding domain (RBD), sits at the top of the spike, where it makes direct contact with ACE2 on human cells. For this reason, some groups are developing vaccines that simply use the RBDeither made as a subunit protein or encoded in mRNA.

RBD-based vaccines could have the advantage of helping the immune system focus on developing neutralizing antibodies to the part of the protein that matters the most. Its also a relatively small part of the large spike protein, which could make these vaccines cheaper to manufacture.

But its small size has drawbacks too. Scientists say we typically develop better immune responses against larger proteins. And researchers are starting to discover neutralizing antibodies that bind to other regions of the spike protein outside the RBD as well, ones that might work by halting the viruss fusion to the human cell, rather than by blocking its binding to ACE2. In general, having neutralizing antibodies to multiple sites should limit the viruss ability to mutate and escape neutralization.

One study in monkeys testing six different DNA vaccines all encoding various versions of the spike protein found that the full-length spike protein induced higher levels of neutralizing antibodies than the RBD. A small study testing four variations of subunit proteins in rabbits found the opposite: the RBD vaccine induced the highest levels of neutralizing antibodies.

The RBD might be good enough. And when you are making a vaccine, you just need to make it good enough, NIAIDs Graham says. But, he adds, we just think it is not quite as good as the whole thing.

Pfizer, which is working with the German mRNA company BioNTech, may be the only group that is hedging its bets by testing multiple vaccines in humans: two encoding the full prefusion spike protein and two encoding the RBD. Although you can do plenty of testing preclinically, some questions you really have to answer in clinical trials, says Pfizers Dormitzer.

If a particular paradigm proves most promising, it will be easy to construct a narrative about why one brilliant group had the right idea all along. You can reason your way into believing that any one front-runner vaccine will rise above the others just as easily as you can convince yourself that one approach is destined for failure. But as it stands, we dont know which vaccines will work the best. Although animal studies can give clues about what wont work in humans, the only way to determine how a vaccine will protect against infection is to test it in people.

III. How will our immune system protect us from the virus?

Key milestones in the rapid design, clinical testing, and funding of vaccines for COVID-19

Jan. 10: The first genome sequence of the novel coronavirus, later named SARS-CoV-2, is posted online.

Jan. 13: Moderna announces plans to develop an mRNA vaccine for the novel coronavirus.

Jan. 23: The Coalition for Epidemic Preparedness Innovations (CEPI) announces vaccine funding for Inovio Pharmaceuticals, Moderna, and the University of Queensland.

March 16: CanSino Biologics and Moderna dose first volunteers in Phase I clinical trials of their vaccines.

March 17: Pfizer announces partnership with BioNTech to develop and test multiple mRNA vaccines.

March 30: Biomedical Advanced Research and Development Authority (BARDA) and Johnson & Johnson announce they are committing more than $1 billion to develop an adenoviral vector vaccine for COVID-19.

April 16: BARDA awards Moderna up to $483 million to develop and manufacture its mRNA vaccine.

April 30: AstraZeneca announces it will develop the University of Oxfords adenoviral vector vaccine for COVID-19.

May 11: CEPI commits $384 million to Novavaxs COVID-19 vaccine, its largest investment ever.

May 15: US President Donald J. Trump announces Operation Warp Speed to supply 300 million vaccines to the US by January 2021.

May 18: Moderna announces preliminary Phase I data from its vaccine trial via press release.

May 21: BARDA says it will provide up to $1.2 billion for 300 million doses of AstraZenecas vaccine with the first shots arriving in October.

May 22: CanSino publishes the first peer-reviewed data of a Phase I COVID-19 vaccine trial.

May 26: Merck & Co. says it will develop two COVID-19 vaccines originally designed at Themis Biosciencean Austrian company that it acquiredand IAVI.

May 29: Moderna doses the first volunteers in its Phase II clinical trial of its mRNA vaccine.

June 20: A Phase III trial testing the University of Oxfords adenoviral vector vaccine begins in Brazil.

June 24: The state-owned China National Pharmaceutical Group (Sinopharm) announces plans for a Phase III trial of its inactivated virus vaccine for COVID-19.

June 28: 10 million people have been infected and 500,000 people have died from COVID-19.

July 7: BARDA and the US Department of Defense sign a $1.6 billion contract with Novavax for 100 billion doses of its vaccine.

All these vaccine efforts are grounded in the notion that producing high levels of potent neutralizing antibodies will prevent the virus from infecting our cells. Measuring those antibodies, however, is fraught with challenges, and we dont even know what levels we should aim for.

Methods used to quantify that neutralizing antibody response are imperfect. Researchers infect cells in a petri dish with either a real or artificial version of SARS-CoV-2 to see how much of the virus is blocked with a particular concentration of antibody-containing plasma. The real and artificial methods yield different results. And, although those results have been cited as rationale for moving COVID-19 vaccines into large, late-stage trials, there is no standard for how these measurements should be reported.

For instance, some groups report the level of neutralizing antibody that inhibits 50% of the virus, while others use higher bars of 80, 90, or 100%. If you make antibodies that neutralize 90% of the virus, that may not be good enough, NIAIDs Graham says. You want a neutralization that is 100% effective.

The number you get depends on the specifics of the assay you run, so comparing one companys numbers to another companys numbers is tricky, Pfizers Dormitzer says. Until we really establish what a protective level of antibodies is, the numbers may be a relative yardstick, but they dont tell you if you are going to have protection or not.

So far, companies have been using as their baseline the levels of neutralizing antibodies found in convalescent plasma of people who have recovered from COVID-19. But research shows that COVID-19 survivors make relatively low levels of antibodies, and one small study suggests they might only stick around for 2 to 3 months.

Credit: Brian Stauffer

Such studies suggest that a vaccine that mimics a natural infection is a pretty low bar. Immunity equivalent to natural infection may not be enough for this virus. It might need to be higher, says David Corry, an immunologist and allergist at Baylor College of Medicine.

On average, each coronavirus has a couple hundred spike proteins that it can use to grab onto a cell, so the number of neutralizing antibodies circulating in our bodies likely needs to be much higher than the number of viruses attempting to establish an infection. If the antibody levels are not high enough, we may end up with only partial protectionwhere we still get an infection, and might even be able to spread the virus to others, but would be safe from progressing to the most severe forms of COVID-19 that hospitalize people.

But even determining the level of antibodies needed to lessen the brutality of the disease is not straightforward. A level of antibodies in one person might send them off without any symptoms at all, while the same level of antibodies in another person may still leave them very sick, Scripps immunologist Dennis Burton says.

Some scientists say that partial protection is a fine goal for the first generation of COVID-19 vaccines. If you can keep people out of the hospital, to me that is a tremendous success, says Gregory Glenn, president of R&D at Novavax. Such vaccines could save lives, and in a hypothetical world where everyone is vaccinated, most individuals could deal with mild cases of COVID-19, and society could return to normal.

Although vaccine makers have focused on neutralizing antibodies, this type of immune response might not last forever. In a study of 191 people tested for cold-causing coronaviruses over a period of 19 months in New York City, researchers found that 9 people were infected with the same virus twice, and 3 were infected with the same virus three separate times. We dont know if either natural immunity or vaccines can prevent these kind of reinfections with SARS-CoV-2. One experiment showed that monkeys who were infected with high levels of SARS-CoV-2 were protected from reinfection 5 weeks lateralthough that study comes with the major caveat that monkeys dont develop full-blown COVID-19 in the first place.

Theres reason to believe that other parts of the immune system, such as T cells, may be important for longer-lasting immunity. Scientists found that people who were infected with SARS-CoV-1, the virus that caused the eponymous severe acute respiratory syndrome (SARS) outbreak in 2003, still had neutralizing antibodies to the virus 2 years after infection, but not 5 years later. In contrast, researchers recently discovered that some people infected with SARS-CoV-1 back in 2003 still have T cells that recognize the virus all these years later.

While antibodies prevent viruses from infecting cells in the first place, T cells can spot cells that are already infected and selectively kill them, thereby halting the spread of the virus. T cells are also better than antibodies at targeting different parts of the virus. Antibodies target proteins on the outside of the virus, which for SARS-CoV-2 is the spike protein. Yet the spike is just one of 27 proteins encoded in the SARS-CoV-2 genome. The other proteins are located inside the virus, or are made by our own cells when the virus is replicating. T cells, unlike antibodies, can learn to spot molecular fingerprints of these proteins in virus-infected cells.

DNA vaccines and viral vectors are better at inducing T cell responses, while subunit protein vaccines primarily induce antibodies. The traditional attenuated virus vaccines that use a live virusand therefore have all those internal proteinsare good at inducing both T cells and antibodies. Every formulation or platform is different, says Surender Khurana, a vaccine scientist at the US Food and Drug Administration. These different platforms can have different kinds of immune responses, and we dont know which immune response is most relevant.

IV. How good is good enough for a COVID-19 vaccine?

Some vaccines, like the one for measles, provide lifelong immunity to nearly every single person who receives them. Others, such as flu vaccines, are needed every year, and even then sometimes only work 30% of the time. For COVID-19 vaccines, the FDA is aiming for something in-between those extremes. The FDAs recently issued guidelines for COVID-19 vaccine development state that the agency expects a vaccine to either prevent disease, or reduce its severity, in at least 50% of vaccinated people.

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What will it take to make an effective vaccine for COVID-19? - Chemical & Engineering News

Women researchers are strongly influencing the adoption of agricultural biotechnology in Africa.

As African women, we are the ones who suffer most whenever drought and food shortages strike, despite the availability of technological solutions to these problems, said Dr. Felister Makini, deputy director general in charge of crops at the Kenya Agricultural and Livestock Research Organization (KALRO).

We are looking for new solutions and how we can use technology to give our people and ourselves better and improved crop varieties to fight hunger and improve the quality of living, said Dr. Priver Namanya Bwesigye, who leads Ugandas banana research program at the National Agricultural Research Laboratories (NARL) at Kawanda. We also need varieties that can give us more in terms of nutrients.

Throughout Africa, women are in labs developing crops that produce high yields and can tolerate or resist disease, as well as healthier, more productive livestock. They are also found in meeting rooms and gardens informing the public about their innovations and how these improved crops can aid the fight against hunger across both the continent and the globe.

It is time to tell the public about the positive side of biotechnology, said Professor Caroline Thoruwa, chairperson for African Women in Science and Engineering.

In Uganda, where bananas are an important staple food and cash crop, Bwesigye is in charge of developing varieties that offer farmers better options.

She and her team are using the tools of genetic engineering to develop banana varieties that are resistant to nematodes, bacterial wilt and weevils. The most advanced of these genetically modified varieties is a banana biofortified to provide vitamin A. It should reach farmers immediately after Uganda implements a legal biosafety framework guiding the use of GMOs.

We have trialled the technology in multiple locations all the four banana planting regions of Uganda and it will be ready by the time we have a legal framework, Bwesigye said. We have to do this [multi-location field trials] before we can give it to the farmers. We want to be sure that different farmers across the country can plant the variety and have similar results. In this case, all the banana yields should be rich in pro-vitamin A.

But Bwesigyes program does much more than develop improved bananas using biotechnology. It also employs conventional plant breeding tools to produce heartier varieties, including a banana resistant to black sigatoka disease. When shes not in the lab, Bwesigye conducts extensive outreach to farmers and young people to explain agricultural biotechnology and why Uganda, Africa and the world need this tool.

Dr. Barbara Mugwanya Zawedde is also championing the adoption of agricultural biotechnology in Africa. Shes currently director for research at Ugandas Zonal Agricultural Research and Development Institute in Mukono, which is under the jurisdiction of the National Agricultural Research Organization (NARO).

But before that, she was the coordinator for the Uganda Biosciences Information Center (UBIC) NAROs knowledge and information-sharing hub. It champions an appreciation of modern biosciences research for agricultural development and works to educate stakeholders on the importance of biosafety.

In that role, Zawedde engaged religious leaders, local communities, farmers, extension agents, legislators, public ministries, women in agriculture, students and others to raise awareness about new technologies and their safety.

After earning a doctorate in plant breeding, genetics and biotechnology from Michigan State University, Zawedde returned home to Uganda in 2013 to discover we had gaps in communication as well as in regulation, she recalled.

So, she worked with Dr. Yona Baguma, now deputy director general for NARO, to set up the biosciences information center. Their goal was to bring to the fore these new technologies that people were not talking about and to emphasise the importance of regulating them.

The regulatory framework [we have been calling for] is not just for the introduction of these new technologies, but for their regulation as well, Zawedde said.

To an extent, Zawedde and UBIC have been successful.

Parliament passed the National Biotechnology and Biosafety Bill on two occasions, though President Yoweri Museveni has yet to sign it into law. Additionally, more Ugandans now appreciate the science and what it can do to improve their lives. Biotechnology and biosafety elements also have been included in the countrys school curriculums.

It will be easier to adopt these technologies [once we have a regulatory framework] because more people today understand these technologies and how they can help improve agriculture and food security in Uganda and the region, Zawedde said

Similarly, the Women in Biosciences Forum is working in Kenya to make everyone sure knows about the value of biotechnology and the role that women are playing to advance the science.

We need to raise the status of women in biotechnology and also encourage women to network in order to achieve the noble goal of sharing their science, Thoruwa said. Women must be involved for Africa to advance in agri-biotech.

Several African countries have approved the cultivation of GMO crops and others have conducted trials for GM crop varieties. But in many of the countries that are conducting research, GM seeds have yet to reach farmers and consumers because the political leadership is swayed by opposition and remains afraid to adopt biotechnology, the women scientists observed.

We need to speak with one voice and advocate for a predictable policy environment, said KALROs Makini.

The detractors will always be there, Bwesigye said. But we need to understand that these technologies, pretty much like everything else in life, have advantages and disadvantages. We just have to harness the advantages.

One such advantage is being able to develop a staple food crop, like a banana, that delivers vitamin A, a crucial nutrient that is lacking in almost 30 percent of Uganda children below the age of 5. It is a no brainer, Bwesigye said about the value of adopting the pro-vitamin A banana.

Despite the political obstacles, Bwesigye and her colleagues remain undiscouraged. Zawedde said that women will continue to conduct communication and outreach, calling on governments to give farmers a chance to plant some of these improved crops.

We only need awareness, awareness and more awareness, Bwesigye said. Then mind-sets will change and adoption of these technologies will be easier.

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African women are leading biotechnology's advance across the continent - Alliance for Science

A college of images of cells, each of which was collected from a 384 well plate using high throughput imaging.

Courtesy of Tanmay Lele

A new faculty member in the Department of Biomedical Engineering at Texas A&M University recently received a multi-million dollar grant to support groundbreaking cancer research.

In May, Tanmay Lele received a $5 million Recruitment of Established Investigators grant from the Cancer Prevention and Research Institute of Texas(CPRIT) to further knowledge about cancer and how it progresses.

Leles research focuses on mechanobiology the mechanical aspects of biology where he works to understand how cells sense external mechanical forces as well as how they generate mechanical forces, and how these mechanical forces impact cell function.

In cancer, both cellular mechanical forces and the mechanical properties of resisting cellular structures go awry. These errors cause abnormalities in cell structure. A particularly striking feature of cancer cells is the highly irregular and/or distended shape of the nucleus.

The nuclei in normal tissue have smooth surfaces, but over time the surfaces of cancer nuclei become irregular in shape, Lele said. Now, why? Nobody really knows. Were still at the tip of the iceberg at trying to figure this problem out. But nuclear abnormalities are ubiquitous and occur in all kinds of cancers breast, prostate and lung cancers.

Pathologists study biopsies and note abnormalities in the shape of the cell and its nucleus to grade the severity of cancer. Lele and his team are computerizing the analysis of nuclear shapes to research the cause of abnormal cancer structures.

Using photos of nuclei and cells in human tissue taken by a pathologist, Leles team has developed a computational algorithm to measure the degree of irregularity in the nucleus. With the algorithm, the team can run statistical analyses of the abnormalities and search for correlations between the extent of the irregularity, changes to genetic or molecular signatures in tumors and, ultimately, patient outcomes.

Leles research aims to help the medical community develop new knowledge of human cancers and how they progress, to better diagnose and manage cancers. Understanding the mechanisms behind the abnormalities can help develop therapies to better treat cancers by targeting the nucleus.

Like any other basic field, we are trying to make discoveries with the hope that they will have long-term impacts on human health, Lele said.

Lele will have two laboratories, one in College Station and one in the Texas A&M Health Science Centers Institute of Biosciences & Technology in Houston. The cancer grant from CPRIT is a collaborative effort with Dr. Michael Mancini and Dr. Fabio Stossi from the Baylor College of Medicine. He said he is looking forward to collaborating with researchers in both College Station and Houston.

Lele received his doctoral degree in chemical engineering from Purdue University. Before coming to Texas A&M, he served as the Charles A. Stokes Professor of Chemical Engineering at the University of Florida. At Texas A&M, in addition to being in biomedical engineering, he will be a joint faculty member in the Artie McFerrin Department of Chemical Engineering.

All my career has been spent in chemical engineering departments, but my research is also now in the biomedical space, Lele said. The move to Texas A&M was an opportunity for me to also be part of a different culture, if you will, of research. Being in the biomedical engineering department, in addition to the chemical engineering department, brings new opportunities to collaborate with researchers who have closely shared research interests.

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Biomedical Engineering Researcher Receives $5 Million Grant To Further Cancer Studies - Texas A&M University Today