Stories about: vaccines

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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Six emerging trends in vaccine development

boy receiving vaccine-shutterstock

Vaccines to protect against infectious disease are the single most effective medical product, but developing new ones is a challenging and lengthy process, limiting their use in developing countries where they are most needed. Once a new vaccine is developed, it undergoes animal testing, which is time-consuming and does not necessarily reflect human immunity.

“It can take decades from the start of vaccine development to FDA approval at huge cost,” says Ofer Levy, MD, PhD, a physician and researcher in the Division of Infectious Diseases at Boston Children’s Hospital. “We are working on making the process faster and more affordable.”

A variety of new strategies are emerging to facilitate vaccine development and delivery:

1. Modular approaches to vaccine production

The Multiple Antigen Presenting System (MAPS) is one innovative modular method to more efficiently produce vaccines that provide robust immunity.

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Hope for the New Year: A dengue vaccine in 2015?

(Photo: CDC Public Health Image Library)

Katherine Broecker is an MPH student at Boston University and a data curator at HealthMap. In this post, which originally appeared on HealthMap’s Disease Daily, she explores the burden of dengue and hopes that a new vaccine will be licensed sometime this year.

What is Dengue?

A virus transmitted by Aedes aegypti and Aedes albopictus mosquitoes, dengue is a flu-like illness characterized by a high fever and severe joint pain, sometimes with hemorrhagic manifestations. There are four distinct serotypes of the virus (DEN-1, DEN-2, DEN-3, DEN-4). Recovery from one infection provides lifelong protection from a homologous (same-strain) infection and partial temporary protection from the other strains. However, subsequent heterologous (different-strain) infection increases the risk of severe dengue manifestations.

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Seeding medical innovation: The Technology Development Fund

Monique Yoakim Turk Technology Development FundMonique Yoakim-Turk, PhD, is a partner of the Technology Development Fund and associate director of the Technology and Innovation Development Office at Boston Children’s Hospital

Since 2009, Boston Children’s Hospital has committed $6.2 million to support 58 hospital innovations ranging from therapeutics, diagnostics, medical devices and vaccines to regenerative medicine and healthcare IT projects. What a difference six years makes.

The Technology Development Fund (TDF) was proposed to Boston Children’s senior leadership in 2008 after months of research. As a catalyst fund, the TDF is designed to transform seed-stage academic technologies at the hospital into independently validated, later-stage, high-impact opportunities sought by licensees and investors. In addition to funds, investigators get access to mentors, product development experts and technical support through a network of contract research organizations and development partners. TDF also provides assistance with strategic planning, intellectual property protection, regulatory requirements and business models.

Seeking some “metrics of success” beyond licensing numbers and royalties (which can come a decade or so after a license), I asked recipients of past TDF awards to report back any successes that owed at least in part to data generated with TDF funds. While we expected some of the results, we would have never anticipated such a large impact.

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Hacking our way to vaccine compliance: The birth of WhatVax

Gomez's team at work on a platform for vaccine tracking and orderingEva Gómez, RN-BC, MSN, CPN, is a staff development specialist in Clinical Education and Informatics 
at Boston Children’s Hospital. She and Tami Chase, RN, nurse manager at Martha Eliot Health Center, received the Springboard Prize from Boston Children’s Innovation Acceleration Program at last month’s Hacking Pediatrics.

For months, my colleague Tami Chase and I had been experiencing a big pain point in our patient-care process: the complicated and time-consuming task of ordering vaccines—a task that requires providers and nurses to memorize or figure out complex algorithms based on variables like patient age, ethnicity and medical/family history. There are many vaccines and formulations, and if vaccine supplies are used incorrectly, we are less able to order free vaccines from federal and state sources. We’re then forced to purchase vaccines privately—tapping hospital funds that could be used for many other worthy projects.

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Leveraging bacteria biofilms for vaccines

biofilm vaccine cholera
Through genetic engineering, this Vibrio cholerae biofilm can be loaded with extra antigens, creating a super-charged but inexpensive vaccine.

Malaria. Cholera. Now Ebola. Whatever the contagion, the need for new, or better, vaccines is a constant. For some of the most devastating public health epidemics, which often break out in resource-poor countries, vaccines have to be not only medically effective but also inexpensive. That means easy to produce, store and deliver.

Paula Watnick, MD, PhD, an infectious disease specialist at Boston Children’s Hospital, has a plan that stems from her work on cholera: using a substance produced by the bacteria themselves to make inexpensive and better vaccines against them.

Cells do all the work

Bacteria produce biofilms—a sticky, tough material composed of proteins, DNA and sugars—to help them attach to surfaces and survive.

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Strengthening newborns’ immune systems: A secret in the plasma

Blood cells
The immunosuppressant effect in newborns' blood comes not from blood cells themselves, but from the plasma that surrounds them (smaller.pathological.ca/Flickr)
There’s something different about newborns’ blood. In babies less than 28 days of age, the immune system still hibernates—making newborns more susceptible to life-threatening infections and less responsive to many vaccines. Ofer Levy, MD, PhD, and his colleagues at Boston Children’s Hospital have done extensive work toward understanding the newborn immune system, and now they’ve uncovered a mechanism to help explain why the system is so weak—and how it might be strengthened.

“If we can understand the molecular mechanisms causing the immune system to be different when we’re very young or very old, we can leverage that knowledge to develop new treatments,” says Levy.

A Lego-like approach to vaccine design

A syringe made of Legos.
A robust, reproducible vaccine with low risk of side effects is hard to come by. A new design strategy could balance the benefits and risks of different vaccine approaches while making them as easy to build as Legos. (seanmichaelragan/Flickr)

A good vaccine should confer robust, long-lasting immunity against a given pathogen without causing side effects. Striking this balance has fueled a long-standing debate over whole-cell and acellular vaccines.

Whole-cell vaccines rely on killed or weakened pathogens. Acellular or subunit vaccines contain only defined sets of antigens known to stimulate an effective immune response against the pathogen in question.

Both approaches have their strengths and weaknesses. Whole-cell vaccines carry a bacterium’s full complement of antigens and can activate many arms of the immune system at once. And they are inexpensive to manufacture. But these vaccines can be hard to reproduce and run the risk of causing frequent or serious side effects.

Acellular vaccines are very reproducible and run a much lower risk of side effects. But the immune responses they trigger aren’t as robust or durable, as evidenced by the recent failures of the acellular pertussis vaccines.

What if you could bring together the effectiveness of a whole-cell vaccine and the safety and reproducibility of an acellular one? That’s what Boston Children’s Hospital’s Fan Zhang, PhD, Yingjie Lu, PhD, and Richard Malley, MD, want to do with the Multiple Antigen Presenting System, or MAPS.

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