The first week of a baby’s life is a time of rapid biological change. The newborn must adapt to living outside the womb, suddenly exposed to new bacteria and viruses. Yet scientists know surprisingly little about these early changes.
Reporting in today’s Nature Communications, an international research team provides the most detailed accounting to date of the molecular changes that occur during a newborn’s first seven days. The team pioneered a technique to extract volumes of data from a tiny amount of newborn blood — including what genes are turned on, what proteins the body is making and what metabolites are changing.
Immunization is one of modern medicine’s greatest success stories. Yet we still lack vaccines for common diseases such as HIV and respiratory syncytial virus. Other vaccines are only moderately effective, like those against tuberculosis or pertussis. The average vaccine can take a decade or more to develop, at a cost of hundreds of millions of dollars, and vaccines that worked flawlessly in mice regularly fail in clinical trials. As a result, many companies are reluctant to enter into vaccine development.
“We need a way to rapidly assess vaccine candidates earlier in the process,” says Ofer Levy, MD, PhD, a physician-scientist in the Division of Infectious Diseases at Boston Children’s Hospital and director of the Precision Vaccines Program. “It’s simply not possible to conduct large-scale, phase 3, double-blind, placebo-controlled studies of every potential vaccine for every pathogen we want to protect against.”
Malaria parasite infection, which affects our red blood cells, can be fatal. Currently, there are about 200 million malaria infections in the world each year and more than 400,000 people, mostly children, die of malaria each year.
Now, studying blood samples from patients treated for malaria at a clinical field station in Brazil’s Amazon jungle, a team of Brazilian and American researchers has made a surprising discovery that could open the door to a new vaccine.
“I noticed that white blood cells called killer T cells were activated in response to malaria parasite infection of immature red blood cells,” says Caroline Junqueira, PhD, a visiting scientist at Boston Children’s Hospital and Harvard Medical School (HMS).
Digging deeper, Junqueira, Lieberman and collaborators have found a completely unexpected immune response to malaria parasites that infect immature blood cells called reticulocytes. The revelation could help to design a new vaccine that might be capable of preventing malaria.
Their findings, published today in Nature Medicine, uncover special cellular mechanisms and properties specific to “teenaged” reticulocytes and a strain of malaria called Plasmodium vivax that enable our T cells to recognize and destroy both the infected reticulocytes and the parasites inside them. …
A new discovery about the spatial orientation and physical interactions of our genes provides a promising step forward in our ability to design custom antibodies. This, in turn, could revolutionize the fields of vaccine development and infection control.
Recent years of research by Alt and others in the field of molecular biology have revealed that it’s not just our genes themselves that determine health and disease states. It’s also the three-dimensional arrangement of our genes that plays a role in keeping genetic harmony. Failure of these structures may trigger genetic mutations or genome rearrangements leading to catastrophe.
The importance of genetic loops
Crammed inside the nucleus, chromatin, the chains of DNA and proteins that make up our chromosomes, is arranged in extensive loop arrangements. These loop configurations physically confine segments of genes that ought to work together in a close proximity to one another, increasingly their ability to work in tandem.
“All the genes contained inside one loop have a greater than random chance of coming together,” says Suvi Jain, PhD, a postdoctoral researcher in Alt’s lab and a co-first author on the study.
Meanwhile, genes that ought to stay apart remain blocked from reaching each other, held physically apart inside our chromosomes by the loop structures of our chromatin.
But while many chromatin loops are hardwired into certain formations throughout all our cells, it turns out that some types of cells, such as certain immune cells, are more prone to re-arrangement of these loops. …
This is part I of a two-part blog series recapping the 2018 BIO International Convention.
At the 2018 BIO International Convention last week, it was clear what’s provoking scientific minds in industry and academia — or at least those of the Guinness-world-record-making 16,000 people in attendance. Artificial intelligence, machine learning and their implications for tailor-made medicine bubbled up across all BIO’s educational tracks and a majority of discussions about the future state of biotechnology. Panelists from Boston Children’s Hospital also contributed their insights to what’s brewing at the intersection of these burgeoning fields.
Isaac Kohane, MD, PhD, former chair of Boston Children’s Computational Health and Informatics Program, spoke on a panel about how large-scale patient data — if properly harnessed and analyzed for health and disease trends — is a virtual goldmine for precision medicine insights. Patterns gleaned from population health data or electronic health records, for example, could help identify which subgroups of patients who might respond better to specific therapies.
According to Kohane, who is currently the Marion J. Nelson Professor of Biomedical Informatics and Pediatrics at Harvard Medical School (HMS), we will soon be leveraging artificial intelligence to go through patient records and determine exactly what doctors were thinking when they saw patients.
“We’ve seen again and again that data abstraction by artificial intelligence is better than abstraction by human analysts when performed at the scale of millions of clinical notes across thousands of patients,” said Kohane.
And based on what we heard at BIO, artificial intelligence will revolutionize more than patient data mining. It will also transform the way we design precision therapeutics — and even vaccines — from the ground up. …
The hepatitis B vaccine is one of only three vaccines that are routinely given to newborns in the first days of life. But the current hepatitis B vaccine has limitations: multiple “booster” doses are needed, and it can’t be given to premature babies weighing less than 2 kg.
Annette Scheid, MD, a neonatologist at Brigham and Women’s Hospital, is interested in leveraging infant immune differences to create a better hepatitis B vaccine for newborns. “The reality is that we have to vaccinate several times,” she says. “But we all dream of a vaccine that you give only once.” …
Boston Children’s Hospital’s Technology Development Fund (TDF)to designed to transform early-stage academic technologies into validated, high-impact opportunities for licensees and investors. Since 2009, the hospital has committed $7.6 million to support 76 promising technologies, from therapeutics, diagnostics, medical devices and vaccines to regenerative medicine and healthcare IT projects. The TDF also assists with strategic planning, intellectual property protection, regulatory requirements and business models. Investigators can access mentors, product development experts and technical support through a network of contract research organizations, development partners and industry advisors.
Eight startup companies have spun out since TDF’s creation, receiving $82.4 million in seed funding. They include Affinivax, a vaccine company started with $4 million from the Gates Foundation, and Epidemico, a population health-tracking company acquired by Booz Allen Hamilton. TDF has also launched more than 20 partnerships, received $26 million in follow-on government and foundation funding and generated $4.45 million in licensing revenue.
Here are the projects TDF awarded in 2017, with grants totaling $650,000: …
To fight HIV, the development of immunization strategies must keep up with how quickly the virus modifies itself. Now, Boston Children’s Hospital researchers are developing models to test HIV vaccines on a faster and broader scale than ever before with the support of the Bill & Melinda Gates Foundation.
The researchers are racing against HIV’s sophisticated attack on the human immune system. HIV, the human immunodeficiency virus, mutates much faster than other pathogens. Within each infected patient, one virus can multiply by the billions. …
Interleukin-1 (IL-1), first described in 1984, is the original, highly potent member of the large family of cellular signaling molecules called cytokines that regulate immune responses and inflammation. It’s a key part of our immune response to infections, and also plays a role in autoimmune and inflammatory diseases. Several widely used anti-inflammatory drugs, such as anakinra, block IL-1 to treat rheumatoid arthritis, systemic inflammatory diseases, gout and atherosclerosis. IL-1 is also a target of interest in Alzheimer’s disease.
Yet until now, no one knew how IL-1 gets released by our immune cells.
“Most proteins have a secretion signal that causes them to leave the cell,” says Jonathan Kagan, PhD, an immunology researcher in Boston Children’s Hospital’s Division of Gastroenterology. “IL-1 doesn’t have that signal. Many people have championed the idea that IL-1 is passively released from dead cells: you just die and dump everything outside.” …
Staphylococcus aureus causes 11,000 deaths annually in the U.S. alone and is frequently antibiotic-resistant. It’s a leading cause of pneumonia, bloodstream infections, bone/joint infections and surgical site infections and the #1 cause of skin and soft tissue infections. Efforts to develop an S. aureus vaccine have so far failed: the vaccines don’t seem to be capturing the right ingredients to make people immune.
Kristin Moffitt, MD, in Boston Children’s Hospital’s Division of Infectious Diseases, took a step back and asked: “What proteins does S. aureus need to make to establish infection?” The answer, she reasoned, could point to new antigens to include in a vaccine.
The above image shows an early result from Moffitt’s investigation. It’s a “heat map” of the messenger RNA signature — a snapshot of the proteins S. aureus is potentially up-regulating during infection. …