Stories about: vaccines

Single-shot protection? Building a better hepatitis B vaccine for newborns

newborn vaccines
(Illustrations: Elena Hartley)

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.”

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Six technologies we backed in 2017

Boston Children's Hospital technology

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:

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Why evolution is the challenge — and the promise — in developing a vaccine against HIV

HIV surrounds and attacks a cell.
HIV surrounds and attacks a cell.

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 field of HIV research has needed a better way to model the immune responses that happen in humans,” says Frederick Alt, PhD, director of the Boston Children’s Program in Cellular and Molecular Medicine, who is leading the HIV vaccine research supported by the 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.

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How do cells release IL-1? The answer packs a punch, and could enable better vaccines

In hyperactivated immune cells, gasdermin D punches holes in the cell membrane that let IL-1 out — without killing the cell.

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.”

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Science Seen: Tackling S. aureus by eavesdropping on infections

S. aureus vaccine messenger RNA transcriptome
This messenger RNA ‘heat map,’ generated from 50 patient samples, shows potential target proteins for a more effective S. aureus vaccine. The color scale indicates the magnitude of the transcription level, with red highest.

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.

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How social media and a mumps outbreak teach us that vaccines build herd immunity

Mumps virus, pictured here, is usually preventable by vaccination.
The mumps virus, pictured here, has been spreading through Arkansas communities. Surprisingly, many affected people say they have received vaccinations to prevent it. Analyzing social media data helped a Boston Children’s Hospital team understand why so many people got sick.

Residents of Arkansas have been under siege by a viral threat that is typically preventable through vaccination. Since August 2016, more than 2,000 people have been stricken with mumps, an infection of the major salivary glands that causes uncomfortable facial swelling.

The disease is highly contagious but can usually be prevented by making sure that children (or adults) have had two doses of the measles-mumps-rubella (MMR) vaccine. But strangely, about 70 percent of people in Arkansas who got sick with mumps reported that they had received their two doses of the MMR vaccine.

So, members of the HealthMap lab, led by Chief Innovation Officer and director of the Computational Epidemiology Group at Boston Children’s Hospital, John Brownstein, PhD, asked, “Why did this outbreak take off?”

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Effective vaccination of newborns: Getting closer to the dream

newborn vaccines global health

In many parts of the world, babies have just one chance to be vaccinated: when they’re born. Unfortunately, newborns’ young immune systems don’t respond well to most vaccines. That’s why, in the U.S., most immunizations start at two months of age.

Currently, only BCG, polio vaccine and hepatitis B vaccines work in newborns, and the last two require multiple doses. But new research raises the possibility of one-shot vaccinations at birth — with huge implications for reducing infant mortality.

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Keeping up with HIV mutations: Building a nimble vaccine test system

AIDS vaccine
A new technology speeds up natural antibody “evolution” to create a nimble HIV vaccine test system. (Images: Wikimedia/Pixabay)

An AIDS vaccine able to fight any HIV strain has thus far eluded science. HIV frequently mutates its coat protein, dodging vaccine makers’ efforts to elicit sufficiently broadly neutralizing antibodies.

Yet sometimes HIV-infected people can produce such antibodies on their own. This usually requires years of exposure to the virus, allowing the immune system to modify its antibodies over time to keep up with HIV mutations. But the goal is generally achieved too late in the game to prevent them from being infected.

“Only a small fraction of patients are able to develop broadly neutralizing antibodies, and by the time they do, the virus has already integrated into the genomes of their T-cells,” says Ming Tian, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM).

Tian is part of a group led by PCCM director Frederick Alt, PhD, that developed a technology to greatly speed up HIV development. Described today in Cell, the group’s method generates mouse models with built-in human immune systems. The model recapitulates what the human immune system does, only much more rapidly, enabling researchers to continuously test and tweak potential HIV vaccines.

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A vaccine of one’s own: Precision medicine comes to immunization

precision vaccines
When it comes to vaccines, one size doesn’t fit all, researchers are finding.

Once upon a time, an English country doctor forged a treatment out of cow pus. Edward Jenner squeezed fluid from a cowpox sore on a milkmaid’s hand, and with it, successfully inoculated an eight-year-old boy, protecting him from the related smallpox virus.

It was the world’s first successful vaccination and laid the foundation for modern vaccinology: researchers formulate vaccines from a dead or disabled microbe — or its virulent components — and people sigh with relief when they don’t succumb to the disease.

But investigators are now finding holes in traditional vaccine dogma. “Vaccines were developed under the assumption that one size fits all,” says Ofer Levy, MD, PhD, a physician-scientist in the Division of Infectious Diseases at Boston Children’s Hospital and director of the collaborative Precision Vaccines Program. “That you develop a vaccine and it will protect the same way whether the patient is young, middle aged or elderly; male or female; living in a city or rural environment; northern or southern hemisphere; whether given day or night; summer or winter.”

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Can we supercharge vaccines? Added compound boosts T-cell production

supercharged vaccines oxPAPCBridging our innate and adaptive immune systems, dendritic cells are sentinels that circulate in the body searching out microbes and activating T-cells to destroy the invaders. They do this by presenting bits of the microbes on their surface—explaining why they’re often called antigen-presenting cells.

Reporting in Science this week, researchers describe a way to push dendritic cells into a “hyperactive” state, supercharging their ability to rally T-cells.

The key player, a fatty chemical called oxPAPC, is naturally found in damaged tissues and atherosclerotic plaques. It selectively targets dendritic cells and could, the researchers believe, enhance people’s immunity to a wide range of infections.

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