Designing a coronavirus vaccine In a related effort, researchers at HMS’s Blavatnik Institute and at the Brigham hope to use an antibody-detection tool called VirScan — which they adapted to recognize antibodies for the novel coronavirus in people’s blood — to help scientists working on vaccines identify which viral antibodies the immune system best responds to and which don’t affect the virus.“[VirScan] can help you follow a vaccine to see how well it’s making antibodies and what kinds of antibodies,” said Stephen Elledge, the Gregor Mendel Professor of Genetics and of Medicine at HMS and Brigham and Women’s, who developed the tool in 2015 with two Ph.D. candidates in his lab. “A lot of the antibodies you make are just useless. They don’t do anything to the virus or hurt the virus and they don’t help it. They’re just neutral. They’re there. Sometimes they even make it easier for the virus to get into certain cell types … The idea would be that you would try to remove them from the vaccine, because they’re competing with the neutralizing antibodies in the vaccine just as much as they would be with the actual virus.”While he hopes this effort takes off, Elledge’s primary focus is on using VirScan as a post-infection tool to study the outbreak’s true extent, lethality, and epidemiology, and learn how the virus affects the immune system.For Barouch, having multiple coronavirus vaccine-related efforts are crucial, since no one group has all the expertise and each vaccine will have pros and cons.“We don’t yet know which vaccine is ultimately going to be the safest, the most effective, and the most deployable,” Barouch said. “Ultimately, if we have two or more vaccines that become available for COVID-19, that would be a good thing because each vaccine is different. For example, some vaccines might be very effective in the elderly; some might not. Some might be easier to produce at mass scale; some might not. Some might be single-dose regimens, some might be multiple-dose regimens. Each vaccine is going to have its own particular characteristics.” A multipronged attack against a shared enemy Harvard scientists take various approaches in the race for a treatment for the deadly coronavirus In Dan Barouch’s lab, many researchers have not taken a day off since early January, and virtually all are working nearly seven days week to develop a vaccine that could help end the coronavirus pandemic.“Everybody wants to contribute to this global crisis as best they can,” said Barouch, director of the Center for Virology and Vaccine Research at the Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School.The team hopes their work will be worth it. There is cause for optimism.The lab developed a vaccine in collaboration with Janssen Pharmaceutical Cos., the drug-making arm of Johnson & Johnson. It plans to launch clinical trials in the fall as part of a joint $1 billion collaboration agreement announced by the U.S. government and Johnson & Johnson on March 30.And the push by Barouch’s group is far from the only one out there. There are currently more than 40 in development around the world, according to the Milken Institute, an independent economic think tank in California. The approaches are varied, but all involve training the body’s immune system to recognize and remember the virus and produce antibodies to fight the disease.Most of the work at Harvard is in its early stages and includes a number of different vaccine methods. Barouch’s lab at Beth Israel is the first to move toward clinical trials so far.Like everyone working on this, “We want to move as fast as we possibly can, because we think the world needs a vaccine,” said Barouch ’93, M.D. ’99 . He co-leads the vaccines working group at Harvard’s Massachusetts Consortium on Pathogen Readiness and is also a steering committee member of the Ragon Institute of MGH, MIT, and Harvard.,A project at the Cambridge biotech Moderna uses the virus’ genetic code to trigger an immune response. It began clinical trials in Seattle on March 16 and was produced in just 63 days. Andrea Carfi, Moderna’s head of research, co-leads the vaccines working group at the consortium with Barouch.Barouch’s lab began working on two vaccines right after scientists from China published the gene sequence of the coronavirus. It’s been a frenzy since.That first weekend, the team quickly identified the protein spike as the target region for a vaccine — the coronavirus gets its name from the crown-like spikes on its surface. By Monday, Jan. 13, they had designs for vaccine constructs and created synthetic viral genes. At the end of the month, the lab started a collaboration with Janssen using one of the company’s approaches. Basically it involves transporting an adenovirus that causes a common cold, coated with coronavirus antigens, into cells to stimulate the immune system to produce antibodies. By Feb. 6, the group started testing the vaccines in animals.Barouch’s lab was able to work so quickly on this method because it has spent the past 15 years working on HIV and, more recently, Zika vaccines using the same approach. The hospital has collaborated with Janssen on vaccines in the past.In mid-February the lab began collaborating with the Chinese Center for Disease Control and Prevention on their other vaccine strategy. That one is DNA-based. Like RNA vaccines, it uses the genetic material of the virus to produce an inoculant that mimics it, helps the body identify it, and create antibodies to fight and neutralize it.At the Precision Vaccines Program (PVP) at Boston Children’s Hospital, Director Ofer Levy, professor of pediatrics at HMS, and other researchers — including David Dowling, an HMS pediatrics instructor — are working toward developing age-specific vaccines.“Most vaccine development disregards species specificity or aid specificity during the preclinical phase,” Levy said. “We’re turning the process on its head. We’re saying who most suffers from coronavirus? It’s the elderly. We take elderly white blood cells, blood donations, test them outside the body, stimulate them with different small molecules called adjuvants [which are added to a vaccine to boost the recipient’s immune response], and then find out which would work best in an elderly individual.”,The group hopes to build a vaccine targeting infants, as well. “Infants can get infected and can have bad outcomes, but also they can spread the infection to others,” Levy said.Their work is supported by National Institute of Allergy and Infectious Disease.In the labs of Mahmoud Nasr and Gerhard Wagner, the Elkan Blout Professor of Biological Chemistry and Molecular Pharmacology at HMS, researchers have just started work on what’s called a subunit vaccine. In these vaccines, scientists only use the essential antigens from a virus, said Nasr, a principal investigator in the renal division and division of engineering in medicine at Brigham and Women’s Hospital.Wagner and Nasr hope to create a vaccine where several copies of the coronavirus spike proteins are placed in large phospholipid nanodiscs that can elicit a strong antibody response by mimicking the large number of spikes of the virus and their position in a membrane. It has been shown that presenting numerous antigens on a membrane environment produces a stronger response than using non-membrane-bound proteins. This method will likely require adjuvants and multiple doses to elicit a strong enough immune response that provides long-term immunity.At Harvard’s Wyss Institute for Biologically Inspired Engineering, researchers hope to create bioactive material that cues a stronger immune response against the coronavirus. They hope the vaccine both kills the virus in infected individuals and helps uninfected individuals develop longer-lasting immunity without the need for additional boosts. Led by David Mooney, a Wyss core faculty member and the Robert P. Pinkas Family Professor of Bioengineering at Harvard John E. Paulson School of Engineering and Applied Sciences, the team previously created cancer vaccines that prompted the immune system to attack and destroy cancer cells. Other efforts at the Wyss focus on diagnostics and therapeutics. “We want to move as fast as we possibly can, because we think the world needs a vaccine.” — Dan Barouch Facing a pandemic, Broad does a quick pivot How the institute converted a clinical processing lab into a large-scale COVID-19 testing facility in a matter of days Researchers prepare for next year and beyond Related
Sign up for our COVID-19 newsletter to stay up-to-date on the latest coronavirus news throughout New York Nassau County police are taking an investigation into a string of armed robberies and a related homicide to the streets.Several members of the police brass joined Nassau County Executive Ed Mangano outside a BP gas station in Jericho on Friday to unveil a giant school-bus sized mobile billboard requesting information that will help an army of investigators find the brazen, gun-toting robber, who has targeted at least 11 businesses, mostly gas stations, in Nassau since mid December.“Nassau County Crime Stoppers needs your help!” the billboard blares in large white letters.Crime Stoppers is offering a combined $35,000 reward—$25,000 for the homicide and $10,000 for the robberies—for information leading to the arrest of the suspect.Mangano, standing at a podium in front of the billboard on the gas station’s property, said police are asking the public to help “bring this cold-blooded killer to justice.”The moving billboard will be driven to the areas where the robberies have occurred, police said. Officials hope this effort will breathe new life into the investigation and perhaps attract the attention of individuals who have crucial information regarding the suspect.“This person has struck every day of the week,” said Chief of Detectives Kevin Smith, describing how the suspect operates. “Our resolve is intact,” Smith added. “It’s not diminished. We’re going to catch this guy.”Police officials are hoping the public can help with their cause.“Don’t hesitate” to call, Smith implored.An armed assailant, pictured in these surveillance images, is believed to be responsible for nine robberies and one homicide since December, police said.The suspect, who is still unknown to police, is responsible for 10 robberies in the county, beginning on Dec. 20 last year and continuing into February. The suspect last struck on Feb. 18, stealing cash from a Sunoco gas station on Hempstead Turnpike in East Meadow.Investigators believe the suspect is also responsible for the fatal shooting of 57-year-old Levittown resident Hany Awad, who was gunned down on Jan. 28 inside the same BP gas station where officials held Friday’s press conference. Police have yet to say what, if anything, was taken from the gas station during the homicide.The suspect is described as a black man between 5-feet, 11-inches and 6-feet tall, with a thin build, wearing all black Nike clothing, a black mask, black gloves, black Nike sneakers with red laces and armed with either a black or a silver revolver. The assailant has hit nine gas stations and two 7-Eleven stores in Westbury, Hicksville, and Jericho. The robbery in East Meadow was the only one committed outside those three neighborhoods.Both the robbery and homicides squads are investigating the crime spree. The Major Case Bureau and Bureau of Special Operations are also assisting in the investigation.Anyone with information regarding these crimes can call Crime Stopper sat 1-800-244-TIPS. All callers will remain anonymous.
The UK’s financial markets regulator is seeking feedback on market structure and regulation to assess whether they reinforce short-termism.The Financial Conduct Authority (FCA) published a discussion paper on primary capital markets in the UK and how they can most effectively meet the needs of issuers and investors.One focus of the paper is potential barriers to the provision of capital for growth, especially for early-stage science and technology companies. The FCA said it “would be useful” to explore the extent to which current market structures and regulation reinforce a short-term focus in issuers and investors, thereby hindering the provision of “patient capital”.The FCA said that discussions with “pre-IPO” companies indicated a need for technical changes to be made to listing rules, but also “raised the question of whether a more fundamental reassessment might be valuable, focusing particularly on ways in which different forms of primary market structure and regulation might better support scale-up and patient capital, which are particularly crucial for early-stage science and technology companies”. It cited concerns that the UK’s primary equity markets were proving less effective at providing a means for companies to raise capital for further growth and development. The regulator said there have been significant changes in secondary capital markets, such as a shift towards algorithmic trading strategies and the separation of primary from secondary markets. These changes were seen by some as having eroded the effectiveness of the primary markets and having led to a focus on short-term trading rather than long-term investment considerations, the FCA said.Market regulation is seen by some as contributing to such a short-term focus, with “trends in market structure and market regulation […] seen by some to be mutually reinforcing”, it added.However, it also said that these views were not shared by all, and that “some stakeholders point to the Financial Reporting Council’s Stewardship Code and the establishment of the Investor Forum as recent improvements to the effectiveness of primary markets in supporting a more patient approach”.“Nonetheless, we are keen in this DP [Discussion Paper] to explore some of the themes that have emerged in this area,” it added.The FCA also asked for feedback as to whether alternative market structures could support “a more patient, long-term approach”, such as a transitional market to sit between fully private and fully public markets.The regulator asked long-term investors to indicate how they value different aspects of the current public equity market model, such as corporate transparency, investor stewardship, corporate governance requirements, or the ability to trade.The FCA also asked for views on whether there is a role for a UK primary debt multilateral trading facility, to encourage more overseas companies to raise debt finance in the UK.The FCA’s discussion paper can be found here.