Posts tagged as:

vaccines

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. Full story »

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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. Full story »

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This 1802 British cartoon skewers the cowpox vacccine, newly introduced against smallpox. Read more at http://en.wikipedia.org/wiki/File:The_cow_pock.jpg#file

This 1802 British cartoon skewers the cowpox vaccine, newly introduced against smallpox. Read more at http://en.wikipedia.org/wiki/File:The_cow_pock.jpg#file

Fifty years after Boston Children’s Hospital faculty developed a vaccine against measles, the United Kingdom is seeing a surge of cases. Last year, it tracked a record 2,000 measles diagnoses—unusual for a country that used to average only a dozen cases every year. With 1,200 cases reported this year so far, that record could be broken.

The cases are the legacy of parents who decided to forgo vaccinating at least 1 million children against measles, based on a 1998 study in The Lancet linking the measles vaccine to autism. That now-retracted study became the origin of its own epidemic, carrying misinformation through a network of parents and media outlets that believed the author had discovered the cause of autism.

Until recently, tracking the spread of vaccine-related rumors was even more difficult than tracking the outbreaks such misinformation engenders. A study in The Lancet Infectious Diseases, involving Boston Children’s Hospital’s HealthMap data collection system and funded by the Bill & Melinda Gates Foundation, has taken a huge step toward turning that around. Full story »

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If we could immunize infants at birth, far more could be protected from infections.(DFID-UK Dept for International Development)

Right now, immunizations against most infections begin at 2 months of age. But that leaves newborns at risk for infections like rotavirus, whooping cough and pneumococcus during a highly vulnerable time.

In resource-poor countries, this is a serious problem: Many children see a health care provider only at birth, so may miss their chance to be protected. Worldwide, each year, more than 2 million infants under 6 months old die from infections, especially pneumonia. If we could immunize infants at birth, it would be a huge win for global health.

Unfortunately, though, newborns don’t respond to most vaccines. Their immune systems are too immature—which is why few vaccines for newborns exist. Full story »

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Bacteria like Pseudomonas aeruginosa (in brown) can move in on critically ill patients or those with cystic fibrosis. Could these bacteria hold the key to their own prevention? (CDC PHIL/Janice Haney Carr)

Putting children on a ventilator is sometimes necessary to save their lives, but it’s not without risks.

Doctors and nurses have to monitor ventilated patients carefully lest the machine over- or underinflate their lungs. Sometimes the very act of putting a child or adult on a ventilator can cause more lung damage (more on this in a future post). And life-threatening pathogens sometimes take advantage of a patient’s weakened state to set up shop in their lungs.

One of them is Pseudomonas aeruginosa, a bacterium long associated with hospital-acquired or healthcare-associated infections (sometimes also called nosocomial infections). Gregory Priebe, MD, and other researchers have spent 40 years trying to develop an effective vaccine against it.

“It’s often resistant to antibiotics, and can be very difficult to treat, even deadly,” says Priebe, a critical care specialist and infectious disease researcher at Boston Children’s Hospital. “People with cystic fibrosis (CF) also get lung infections with P. aeruginosa, where it can lead to a chronic and ultimately fatal infection.”

While there have been some limited successes in creating a vaccine, researchers have struggled to develop one that can work against multiple subtypes of the bug at the same time.

Priebe thinks he may have come up with a workaround—one that makes use of a little known arm of the immune system. Full story »

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Efforts to create a malaria vaccine have had limited success. Springer and colleagues solved the 3D structure of a key protein on the parasite -- and found a fragment which they'll soon test as a vaccine. (Photos_by_Angela/Flickr)

From the perspective of a wealthy country, malaria is a problem that is solved. It’s like smallpox. We ask, Who gets it?  Who cares? Isn’t it better to invest in diabetes?

In truth, malaria is more infectious than ever, endemic to 106 nations, threatening half the world’s population and stalling economic development and prosperity.

That’s part of the reason why Timothy A. Springer, PhD, an investigator in the Program in Cellular and Molecular (PCMM) Medicine at Boston Children’s Hospital and the Immune Disease Institute (IDI), took on Plasmodium falciparum, the parasite that causes malaria. Another is that he likes solving problems in immunology – and has made his name discovering molecules that both promote and fight infections, in part by understanding their structures. Full story »

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Influenza A H1N1 model (scherle.com/Wikimedia)

What caused previously healthy children to die during the 2009 H1N1 influenza pandemic?  Yesterday, the journal Pediatrics published the results of a study I conducted with the Pediatric Acute Lung Injury and Sepsis Investigator’s (PALISI) Network. Results have been widely reported, by the New York Times, the Washington Post, USA Today and TIME, among many others, provoking a lot of reader commentary, questions and, I fear, some misconceptions.

Methicillin-resistant S. aureus (MRSA)(CDC)

Our study collected data on 838 children with 2009 H1N1 infection admitted across 35 pediatric intensive care units (ICUs) in the U.S. Most of these children were severely ill, the majority requiring mechanical ventilator support for respiratory failure, and 9 percent died. Many  (70 percent) had underlying illnesses like asthma or neurologic conditions that increased their risk. But among those who were previously healthy, the chief risk factor for death was co-infection with methicillin-resistant Staphylococcus aureus, or MRSA. It increased the risk of mortality 8-fold. Full story »

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Streptococcus pneumoniae in spinal fluid

Streptococcus pneumoniae in spinal fluid

Serious pneumococcal infections – pneumonia, bacteremia, meningitis – are responsible for up to 11 percent of child deaths on the planet. Vaccines exist, such as Prevnar, but they have two big shortcomings.

First, they’re designed to help people build antibodies against specific strains of pneumococcus. But new strains keep emerging, and most of those circulating in the developing world aren’t covered.

Second, they’re too expensive for most developing countries.

Six years ago, Richard Malley, of the Division of Infectious Diseases at Children’s Hospital Boston, and Marc Lipsitch of the Harvard School of Public Health, showed that there is another defense against pneumococcus that doesn’t care what strain it’s encountering. And, despite what textbooks were saying, it has nothing to do with antibodies. Full story »

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Streptococcus pneumoniae kills over a million young children a year, most of them in the developing world. Yet currently available pneumococcal vaccines are only effective against strains circulating in Europe and the US.  How can we make affordable vaccines that work globally? Full story »

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Ofer Levy is nothing if not passionate. Talking about his new project, he starts taking notes on my pad for me, to make sure I catch every detail. When Levy was getting his MD/PhD at NYU, one of his mentors told him, “In pursuing your life’s passion as a researcher, you should set your sights on a distant star.” Full story »

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