Working towards a life-long, universal flu vaccine

Photo by Blake Patterson
Photo by Blake Patterson

To prepare for holiday socializing, I always roll up my sleeve to get an annual flu shot. I would much rather share food and gifts than a virus with my friends and family. And I don’t want to spend my precious vacation time sick.

However, seasonal flu vaccines are not always effective. There are thousands of strains of influenza virus and each can mutate over the course of the flu season. Seasonal vaccines only protect against a few of the most likely strains. As a result, flu-associated deaths range from 3,000 to 49,000 Americans per flu season, according to the Centers for Disease Control and Prevention.

Scientists have long-sought a life-long vaccine that would be effective against any variety of influenza, and they are now making significant progress towards this goal.

I recently spoke with Ian Wilson, PhD, a leading structural and computational biologist at the Scripps Research Institute, about his team’s universal flu vaccine research. He told me:

Our research has identified a good target for such a vaccine on a protein called hemagglutinin (HA) that is present on the surface of all influenza viruses. The HA protein has two major components: the head portion, which mutates and varies from strain to strain, and the stem, which is similar across most flu strains. We know that the HA stem is the virus’s most vulnerable spot, and provokes the greatest breadth of immune response. So a synthetic version of the stem was designed, called a mini-HA that mimicked the HA stem.

A key part of Wilson’s flu research took place at the Stanford Synchrotron Radiation Lighsource at the SLAC National Accelerator Laboratory, where the scientists used a technique called X-ray crystallography to look at the atomic structure of the mini-HA at each stage of its development. I wrote a recent news article about the work.

Though this is important research, more work needs to be done. “We still need to perform human trials and also want to develop a vaccine that protects against all types of influenza that cause human pandemics,” said Wilson.

The is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Berkeley Lab Tackles Vaccine Delivery Problem with Portable Solar-Powered Vaccine Fridge

LBNL Institute for Globally Transformative Technologies research team with prototype vaccine fridge and backpack for developing countries. (Berkeley Lab / Roy Kaltschmidt)
LBNL Institute for Globally Transformative Technologies research team with prototype vaccine fridge and backpack for developing countries. (Berkeley Lab / Roy Kaltschmidt)

Vaccines are arguably one of the most important inventions of mankind. Unfortunately, vaccines must be produced and stored in an environment with very tight temperature regulation – between 36 °F and 46 °F – to keep the vaccine bugs alive. So vaccine delivery is a major problem due to the absence of reliable refrigeration in many remote countries.

Approximately 30 million children worldwide – roughly one in five – do not receive immunizations, leaving them at significant risk of disease. As a result, 1.5 million children under the age of five die annually from vaccine-preventable diseases, such as pneumonia and diarrhea. Perhaps more surprising, almost half of the vaccines in developing countries are thrown away because they get too warm during delivery so they are no longer viable. Some administered vaccines are also ineffective because they froze during transport, but there is no easy way to test this.

Scientists at Lawrence Berkeley National Laboratory (LBNL) are trying to solve this vaccine delivery problem by developing a portable solar-powered fridge. Fabricated entirely at LBNL, their portable solar-powered vaccine fridge will be transported by bicycle or motorcycle in remote areas of the developing world. Zach Friedman and Reshma Singh are leading the project as part of the LBNL Institute for Globally Transformative Technologies, which seeks to bring scientific and technological breakthroughs to address global poverty and related social ills.

The team’s first prototype portable fridge uses a thermoelectric heat pump, rather than a traditional vapor compression heat pump that relies on a circulating liquid refrigerant to absorb and remove heat. The thermoelectric chips were initially developed to keep laptops cool, so laptops could be made thinner without fans. The technology was adapted for this global application to reduce the size and weight of the fridge.

Their portable units have a one to three-liter capacity, much smaller than standard solar fridges that are typically 50 liters or more. Once the fridge cools down to the right temperature (36 °F – 46 °F), it is designed to run within that temperature range for at least five days without any power, at an ambient outside temperature as hot as 110 °F.

Before the researchers can field test their first prototype fridge in Africa, they need to pass the World Health Organization’s Performance, Quality and Safety testing protocol for products used in immunization programs. They are currently busy performing in-house testing at LBNL to ensure that they pass the formal tests, which will be conducted by an independent laboratory in the UK.

“We aren’t in the process of field testing yet, but we have established field testing agreements in both Kenya and Nigeria and have locations identified,” said Friedman. “We expect to start testing this coming year.”

Meanwhile, they are continuing their portable fridge development. “Currently, we are pursuing both thermoelectric and vapor compression heat pumps, even for these smaller devices,” explained Jonathan Slack, lead engineer. “It is not clear which will win out in terms of manufacturability and affordability.”

They are also developing a backpack version of the vaccine fridge. However, human-carried devices have to meet stricter World Health Organization standards, so they are focusing at this stage on the small portable fridge instead.

Ultimately their goal is to make it easy for health care workers to deliver viable vaccines to children in remote areas, solving the “last miles” of vaccine delivery.

This is a repost of my KQED Science blog.

Hope for an anti-Nicotine Vaccine

Photograph courtesy of Ianier67 via Creative Commons.

A friend once told me that it was 100 times harder for him to quit smoking cigarettes than to quit drinking alcohol. He was successful and hasn’t smoked a cigarette for over 10 years, but he’s a lucky minority. I have several other friends who still struggle with smoking cigarettes – willpower, counseling, exercising, nicotine replacement patches and antidepressants like Zyban haven’t been enough.

Clearly nicotine is highly addictive. About 45 million people in the U.S. smoke cigarettes, even though cigarette smoking leads to 1 of every 5 deaths each year. In a National Health Interview Survey, over half of the smokers reported trying to quit in the past year without success.

In the future, these smokers may get a vaccine to help protect them from nicotine addiction.

Researchers from Weill Cornell Medical College and Scripps Research Institute have developed a new vaccine that may treat nicotine addiction, by blocking the pleasurable sensations that nicotine creates in the brain. Dr. Ronald Crystal and his colleagues have demonstrated that they can prevent nicotine from reaching the brain in mice using a single injection of vaccine. If these findings are confirmed in people, this vaccine could be an effective therapy to help prevent nicotine addiction.

For more information about this research, check out my KQED Quest blog.

FDA Approves Prostate Cancer Vaccine

How much is 4 months of your life worth? Some men with advanced prostate cancer will be able to find out, as a result of a new drug developed byDendreon Corporation. This drug, Provenge (sipuleucel-T), was recently approved by the FDA to treat advanced prostate cancer.

They are calling Provenge a “vaccine,” but it doesn’t work like vaccines against infections such as measles or mumps. This vaccine is used to treat advanced prostate cancer rather than prevent it. It works by using the patient’s own immune system. The vaccine is made by taking a sample of the patient’s blood, removing the white blood cells, and exposing them to the Dendreon PAP-GM-CSF protein. This specialized fused protein includesprostatic acid phosphatase (PAP), which is an enzyme produced by the prostate and found at increased levels in prostate cancer. Once the vaccine is made, the cells are then infused back into the patient’s vein. The patient receives three of these treatments, 2 weeks apart. Basically the treated cells help stimulate the patient’s immune system to attack his prostate cancer.

The FDA approval of this new vaccine was largely based on the results of Dendreon’s recently completed Provenge Phase III Trial. This was a randomized clinical trial involving 512 men between the ages of 40 and 91 years, of which 341 men received Provenge and 171 men received a placebo. All the men had advanced prostate cancer that was unresponsive to hormone therapy. The common side effects of the Provenge were reported to be minor — such as chills (54%), fevers (29%), and headaches (16%) — and only lasted a couple days after infusion. The men that received the Provenge on average lived 4.1 months longer than the men that took the placebo (25.8 months v.s. 21.7 months). This is a significant break through for men with advanced prostate cancer, who have few treatment options.

There was no evidence that Provenge slowed progression of the disease. How the drug can improve survival rate without slowing disease progression is not clear yet. The FDA approval of Provenge is also limited to only men with prostate cancer (that has progressed despite hormone treatments) with only minimal symptoms at the time of treatment. So this vaccine is not for everyone with prostate cancer. However, it is the first active immunotherapy to demonstrate improvement in overall survival for advanced prostate cancer. As a “proof of concept” drug, it is expected to spark new interest in the development of drugs based on similar principles.

Other prostate cancer vaccines are also in development, including PROSTVAC-VF that uses a genetically modified virus containing prostate-specific antigen. The patient’s immune system is expected to respond to the virus by recognizing and killing the cancer cells with prostate-specific antigen. A randomized phase II clinical study of Therion Biologic’s PROSTVAC-VF was published this January. It involved 122 patients with metastatic prostate cancer who did not respond to hormone therapy, of which 82 received the vaccine and 40 the placebo. This study also demonstrated an increase in survival rate for those taking the vaccine, in this case an average of 8.5 months. This study is small, but the researchers are planning a phase III trial with 600 patients to further evaluate the drug’s effectiveness.

So lets hope that these new drugs represent only the first step in finding effective new ways to treat cancers. In the future, hopefully we’ll be able to “turn on” the body’s own defense mechanisms to treat or prevent many types of cancer.