Universal Flu Vaccine One Step Closer

For the millions of people around the world who suffer each winter from flu, and especially for those with weak immune systems, such as, children, the elderly and pregnant women there is promise of a new “super vaccine.”

Scientists from Switzerland’s Institute for Research in Biomedicine (IRB) just announced that they have isolated and identified a human antibody – F16 –  that can knock out all influenza A viruses. Tests in mice showed it was effective.   This represents an exciting step forward in the hunt for a universal vaccine.

Currently, in what amounts to little more than a scientific lottery, virologists have to play catch-up as they develop a new flu vaccine cocktail each season to match the often-changing strains of the virus.

F16, could help change all that. “The antibody works not only by neutralizing the virus, which we knew, but also by recruiting killer cells to the virus-infected cells,” said Antonio Lanzavecchia, director of IRB.

By observing the human immune response to the 2009 H1N1 flu pandemic he became convinced that it would be possible to design a vaccine that prevails over mutation.   “We found some people with antibodies to multiple viral sub-types.” Antibodies, which are produced by white blood cells, bind to specific target sites inactivating viruses or flagging them for destruction by other immune cells.  To test the cross-reactivity of influenza antibodies, the team screened B cells from eight human donors who had been infected with or immunized against different flu strains.  After looking at 104,000 B cells, they hit the jackpot!

Our FI6 antibody is the first one ever found that reacts to all 16 of the influenza A subtypes,” said Lanzavecchia.

Finding antibodies to all strains of one group was exciting,” says immunologist, Patrick Wilson from the University of Chicago, Illinois, who was not involved with the study, “but getting one to both groups is stunning.”

The F16 antibody is not a vaccine, but it could be an instruction manual for making one.  And although the scientists admit that making a new vaccine may take years, they hope that the antibody itself might be used as a treatment in the meantime. So far, tests in animals have shown that when the antibody binds to the virus, it stops it from infecting mammalian cells.

Once tested in a human system, the antibodies should work even better.  However, even reducing the viral load by 10% could help stop people getting sick.

SRxA’s Word on Health looks forward to having one less thing to worry about in winter.

Loss of a Legend

SRxA’s Word on Health is mourning the loss of a great physiologist and a dear friend. Professor John Widdicombe, one of the worlds foremost authorities on cough passed away on Thursday, 25th August after a brief illness.

A few weeks ago I was privileged to interview him for Cough It Up!  At the time neither of us dreamed that these could be his last published words.

As a tribute we are reproducing the article in its entirety. While the interview includes many touching insights into his life and personality, perhaps more telling was his response to it. Within hours of receiving the draft he got back to me, despite a 5 hour time difference and the fact he was leaving for a months vacation in France that very day.  In his email, he commended my efforts and gave his approval to publish but added: “I would have preferred to seem more modest, but then perhaps I am not.”

So modest, so generous and so inspiring to the end. Professor Widdicombe will be sorely missed, not just by his wife and family but by the legions of doctors, researchers and students whose lives he touched over the years.  In the short time I knew him, he taught me to be a better person and reminded me you are never too old to learn.

Rest in peace, my friend.  The world just lost a great man but heaven gained an awesome teacher…and student.

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Words of Wisdom

During the course of the 2011 American Cough Conference, Cough It Up!  was privileged to sit down with one of the all time greats of the cough world.  In a remarkably frank interview, Professor John Widdicombe shared with us some of his thoughts on cough past, present and future.

In your research career spanning over 60 years who or what has been the biggest influence?

Without a doubt it’s been the people I have been fortunate enough to work with over the years. Mentors, colleagues and students have all influenced me.

How did you get started in cough research? 

I started research in 1950 at the Nuffield Institute for Medical Research in Oxford.  In those days it took only 4 weeks to get a licence to do animal experiments. While I was waiting I was told to go to the library and read up the physiology of the oesophagus ‘the most neglected tube in the body’, and also to learn German. After a month I returned to my boss and told him “No-one, including me, is interested in the oesophagus. The tracheobronchial tree is an even more neglected tube and far more interesting. Can I work on cough and respiratory reflexes?” He agreed, and cough and airway physiology and pathophysiology have been my main research interests ever since.

How has our knowledge of cough improved since you started your research career?    

In 1953, when I was writing my doctorate thesis I could only find six references on cough sensory mechanisms. Now hundreds or thousands are quoted in Pubmed (depending on your question). Before 1996 there was only one monograph on cough (Korpas and Tomori, 1979) and there had been no international symposia. Now there are at least 10 books, including monographs, and one or two international symposia are held each year on the subject. I am happy and proud to have been part of this expansion of interest. We all cough, many of us suffer from it, and we are beginning to understand why.

What has been your biggest achievement in cough research?

I think that what, some decades ago ago, seemed rather a simple reflex, like the stretch reflex or the blink reflex, turned out to be extremely complex. Sorting out some of its complexities has been of great scientific interest and also, I hope, of help to patients.

What further developments in cough research would you like to see in your lifetime?

At present, treatment of cough is like treating headache with a rubber hammer to the head. I would like to see development of drugs known to act on particular components of the cough mechanism, and ‘specific’ to particular types of cough.

What’s the greatest piece of advice you’ve been given during your career?

Geoffrey Dawes, my mentor back in the early days at Oxford, told me Language is the first tool of the scientist.”  This so true.  If you don’t understand your language then you don’t know what you are talking about.

And the worst?

Geoffrey also told me “German is the language of science.”  That was not true even in 1950. Still, I’m glad he taught me this; it led to me translating the Bismarckian German of Breuer and Kratchsmer and discovering their genius in spite of the fact that they didn’t seem to know that cough existed.

What is the one piece of advice you would give to someone starting out in cough research today?

I am not sure that I would give advice, except to say they must be enthusiastic. I would also suggest that then spend four weeks or more in the library before making up their minds!

What was your biggest take-home message from the 2011 American Cough Conference?

That there was wonderful extension and dissemination of information on cough, and great advances are being made.

You officially retired almost 20 years ago, but here you are at the Cough Conference, still moderating sessions and still writing papers on cough. Why?

When I retired I made a number of firm resolutions. Since then, I have broken them all! While retirement should have been the end of cough for me, my friends and colleagues would not allow this. In my retirement I think back to my 1968 ‘sabbatical-in-residence’ at Oxford, during which time I contracted viral pneumonia.  It lasted about a week and led to three chance observations. Firstly, after that episode I always coughed on forced deflation. This is well known clinically but had never been studied until Giovanni Fontana and colleagues did so in 2010. Their paper (Lavorini et al, 2010), on which my name proudly sits, is the first mention of deflation cough in the literature.  Secondly, the sensation of collapsed lung tearing open is quite well known clinically (Macklem, 1968, personal communication), but nobody has identified its afferent pathway. It is not cough, pain, irritation or dyspnea. I still ask myself, do we have Velcro receptors in the lungs?  Thirdly, ever since that pneumonia I have had mild attacks of ‘chronic cough’ every year or two. I think the virus is sitting in my lungs like herpes can in the skin, waiting to break out. My clinical friends tell me this is nonsense, but I’d like to see some evidence before I abandon my theory.

Tell us about your happiest memory

One of the happiest and most memorable events in my life was organized by my wife and family. To celebrate my 80th birthday, they invited family, friends and colleagues from all over the world to a beautiful venue inIreland.  Over dinner, cough was mentioned frequently.  Songs, limericks and anecdotes were even devoted to it, but always as a joke. On that occasion we got our priorities right.

Thank You Professor Widdicombe, it was a pleasure chatting to you.

Roll Up Your Kids’ Sleeves, Before Going Back to School

There are only two things a child will share willingly,” renowned pediatrician Benjamin Spock once wrote, “communicable diseases and his mother’s age.”

While you can’t control what your little darling will say, you do have a little more control when it comes to his or her health. Whether your child is learning the alphabet or learning to drive, back to school check- ups are a great way for parents to make sure their kids are protected against disease and illness. Vaccination is one of the many important procedures performed during such check-ups. Not only does it  protect your child from acquiring potential serious diseases but also it can protect your community.

With that in mind, and the back-to-school season upon us, SRxA’s Word on Health is pleased to bring you the following information:

Vaccination requirements vary by state and school district. You can contact your local school board to find out exact requirements.

The Center for Disease Control and Prevention (CDC) recommends the following immunizations for children 0-6 years:

  • Hepatits B Vaccine (HepB)
  • Rotavirus Vaccine (RV)
  • Diphtheria and tetanus toxoids and acellular pertussis vaccine (DTap)
  • Haemophilus influenzae tybe b conjugate vaccine (Hib)
  • Pneumococcal vaccine (PCV and/or PPSV)
  • Inactivated poliovirus vaccine (IPV)
  • Influenza vaccine (seasonal)
  • Measles, mumps and rubella vaccine (MMR)
  • Hepatitis A vaccine (HepA)
  • Meningococcal conjugate vaccine, quadrivalent (MCV4)

For children aged 7-18 years, the CDC recommends the following immunizations:

  • Tetanus and diphtheria toxoids and acellular pertussis vaccine (Tdap)
  • Human papillomavirus vaccine (HPV)
  • Meningococcal conjugate vaccine, quadrivalent (MCV4)
  • Influenza vaccine (seasonal)
  • Pneumococal vaccines
  • Hepatitis A vaccine (HepA)
  • Hepatitis B vaccine (HepB)
  • Inactivated poliovirus vaccine (IPV)
  • Measles, mumps and rubella vaccine (MMR)
  • Varicella vaccine

Maybe the thought of all those needles will keep your little one from revealing your age!

Pharma Ads Under Fire

Although the back-to-school season has barely begun, both the pharmaceutical industry and the FDA have already received “could do better” report cards. According to researchers from Mount Sinai School of Medicine, only 18% of 192 pharmaceutical advertisements in biomedical journals were compliant with FDA guidelines.  And, over half failed to include serious risks including death. The study, was the first in almost 20 years to provide a systematic assessment of the adherence of US pharmaceutical ads to FDA guidance. Researchers looked at prescription pharmaceutical ads published in nine major peer-reviewed journals, including: the Annals of Internal Medicine,  Blood,  JAMA and the New England Journal of Medicine, during the month of November 2008.  They evaluated adherence to FDA standards and the presence of safety information.  Of the 192 advertisements for 82 unique products, only 15 fully adhered to all 20 FDA Prescription Drug Advertising Guidelines. Advertisements contained bias with regard to a wide variety of issues:

  • 57.8% of the advertisements did not quantify serious risks
  • 48.2% lacked verifiable references
  • 28.9% failed to present adequate efficacy quantification

However, despite the high rates of FDA non-adherence, the mean number of biased features in each advertisement was low and most advertisements they reviewed satisfied the majority of FDA guidelines. Part of the problem it seems is that the FDA emphasizes avoiding frankly false information and balancing efficacy and safety information  but does little to encourage the presentation of useful and accurate information.  For example, an ad containing no specific efficacy claim, no quantification of drug safety and no verifiable references would adhere fully to FDA guidelines, despite presenting no practical information for clinicians.

Dr. Deborah Korenstein, lead author of the study and Associate Professor of Medicine at Mount Sinai School of Medicine is concerned by the lack of adherence. “While the majority of physicians deny that advertisements inform their prescribing marketing research has consistently shown that journal advertising is the most profitable form of drug marketing, with an estimated return on investment of $5 for every dollar spent.” She does however acknowledge that it may be unrealistic to expect  ads to inform rational prescribing by presenting complete drug safety and efficacy, since they primarily serve a marketing function and are not designed to train physicians to prescribe.  Her advice?  “Physicians should ensure that their prescribing is informed by the clinical literature and not by marketing materials.” She also notes that the findings have important policy implications. Although he FDA has already demonstrated a desire to improve the quality of pharma ads, by enlisting doctors to review advertisements through its “Bad Ad” program, Korenstein suggests that the current FDA guidelines are subjective, challenging to enforce and do not emphasize transparency and the inclusion of basic information relevant to prescribing. She suggests that the FDA should update and simplify its guidelines for physician ads. According to her, guidelines should be straightforward and objective. They should ensure that ads present clear risk quantification, absolute benefit information, description of the appropriate population to receive the drug, and verifiable references to published peer-reviewed  literature. In other words, the FDA may hold the key to improving the quality of pharmaceutical advertisements rather than the industry itself.

Chronic Disease on the Catwalk

Chronic disease plagues personal lives and public policy. Sheer numbers only begin to give a glimpse of the associated suffering, cost and scope of the problem. In the United States there are more than 110 million Americans with a chronic disease. Europeans are not far behind. According to the World Health Organization, the chronic disease burden in Europe is now the leading cause of mortality and morbidity. Diabetes, cardio-vascular disease, just to name a few, pose a growing challenge to populations throughout Asia-Pacific, Africa and South America.

As the world’s population ages and the number of older adults multiplies we can anticipate growth in the rate as well as the number of people with chronic diseases such as arthritis and hypertension. We will also see growth in diseases that are only now receiving broader public attention, e.g., Alzheimer’s disease, depression, even some types of cancers that are being redefined as a chronic condition.

Will chronic disease become so prevalent that it becomes the new normal? It just might and here are some early indications. Disease, or rather the number of people managing one condition or more, is now a large enough market to influence the design and fashion industries to develop new medically-inspired products. For example: Bang & Olufsen the Danish, high-end design company invested in Medicom. Bang & Olufsen Medicom designs and manufactures intelligent compliance devices for asthma and diabetes. Not surprisingly, their inhalers and glucometers are anything but ordinary.  Medicom claims they seek to use intelligent technology such as smart devices that connect via bluetooth to the internet/cloud and elegant design to motivate and even “inspire” both physician and patient while reminding and encouraging compliance. Medicom’s injection systems and pill boxes appear to be more like stylish desk ornaments  than tools to treat a chronic medical condition. Medically-inspired yet fashionable products to manage disease and well-being are going mainstream.

A quick trip to stores such as Brookstone shows the growing demand for products to treat the maladies of stress, fatigue and pain. Some Apple stores already have third-party stylish iPod-ready devices to monitor blood pressure, pulse rate, etc. Glasses are no longer thought of as vision correctors, instead they have become a fashion accessory. Mainstreaming disease and producing products that are fashion statements may be dismissed by many as a waste of money or in poor taste given the dire impact of disease on people and economies.  However, given the suffering as well as economic cost of the chronic disease challenge, maybe it’s not a bad thing if we can look a little cooler along the way.

Most Docs Not impressed by Reps Wielding iPads

While the iPad may be the hottest “must have” gadget for pharma sales reps, most doctors aren’t quite so thrilled when they are whipped out during presentations.

According to Manhattan Research while 38% of the 1,755 physicians surveyed have seen a pharma rep use an iPad or other tablet during a face-to-face meeting in the last 12 months, only 36% of physicians find the experience to be more beneficial than speaking with reps who use print materials or devices, such as laptops.

General surgeons, infectious disease or HIV physicians, anesthesiologists and OB/GYNs are the specialty groups that are most likely to agree sales reps should use iPads or other tablets for product discussions during office visits.

In contrast, rheumatologists and dermatologists are less inclined to feel that tablets are needed.

iPads are all the rage for pharma at the moment, which makes sense given the potential of these devices to support intelligent, nimble sales conversations,” says Monique Levy, VP of Manhattan Research. “Unfortunately, some of the detailing programs that are being rushed out the door are sub-par – really no better than something you’d see on tablet PCs six years ago. Doctors won’t waste their time with these.”

Despite this survey, Word on Health doesn’t expect to see reps giving up their high priced status symbol “toys” just yet. In fact, we’re pretty sure that the iPad is here to stay along with those other rep essentials – iPhone, expense account and shiny new car.

The challenge then is to create engaging medical apps and programs for the iPad.  SRxA can help companies do just that.  Contact us for more information and see how we can put the iPizzaz into the iPad!

Want a healthy baby? Buy a dog!

Calling all prospective parents. Want to reduce the risk that your child will be one of the 1:5 who develop allergies?  Seems you should get a dog or cat first and then opt for a natural delivery.

According to a groundbreaking study just published in the Journal of Allergy and Clinical Immunology, researchers from Henry Ford Hospital found that babies who are exposed to pets during pregnancy, and those who were delivered vaginally rather than by cesarean section, have lower levels of the antibody – IgE.

The production of IgE in response to innocuous substances is the hallmark of allergic disease. As more IgE is produced, total IgE levels increase. High total IgE levels are associated with an increased risk for asthma and allergies in children.

The study showed that the levels of IgE were 28% lower in babies exposed to indoor pets in the womb than those from pet free homes and 43% percent lower in infants who had both prenatal pet exposure and were delivered naturally.

The findings support the so-called “hygiene hypothesis”, which theorizes that early childhood exposure to infectious agents affects the immune system’s development and onset of allergies and asthma.

We believe having a broad, diverse exposure to a wide array of microbacteria at home and during the birthing process influences the development of a child’s immune system”, says Christine Cole Johnson, Ph.D., MPH, chair of Henry Ford’s Department of Public Health Sciences and senior author of the study.

She theorizes that indoor pet exposure has a protective effect against early allergy development and that babies born through the birth canal are exposed to a higher and more diverse burden of bacteria, further boosting the immune system’s protection against allergies.

SRxA’s Word on Health thinks it’s kind of ironic that pets are good for you before you’re born, yet are the second leading cause of allergies afterwards!  Let us know what you think.


Are Isolation and Ice-Cream Bad for Your Breasts?

Do you often curl up alone in your room with a bag of potato chips or a gallon of ice cream?  After reading this, you may want to think again. According to researchers at Georgetown’s Lombardi Comprehensive Cancer Center, stress from social isolation and a high-fat diet increase levels of a brain neurotransmitter that promotes obesity, insulin resistance and breast cancer risk. The findings of the study, were reported at the 2011 American Association for Cancer Research(AACR) Annual Meeting. The study compared 4 groups of mice:

  • a group that lived together (not socially isolated) and ate a normal diet;
  • a group that was isolated (each alone in a cage) and ate normally;
  • an isolated group that ate a high-fat diet;
  • a group that lived together and ate a high-fat diet.

Results showed that the mice that were isolated and given a high-fat diet developed a major increase in the level of the neurotransmitter NPY.  At the end of 17 weeks 92% of the mice in this group had developed cancers. Mice that were isolated for two weeks but fed a control diet also had elevated neurotransmitter levels but, the tumors that developed in the high-fat, socially isolated mice appeared earlier and were larger than in the other groups. The researchers say their findings appear to link to a number of findings in humans, such as the fact that social isolation is associated with an increased risk of cancer development and mortality, and that obesity is a risk factor for breast cancer. Although they suspect that NPY may play a role in development of human breast cancer, there is currently no evidence for such a connection because human studies have not yet been done. “We have yet to translate these findings to humans, but it does suggest that social isolation is a potent stressor and initiates a robust central nervous system response,” says Allison Sumis, a Ph.D. student in GUMC’s tumor biology program.

I don’t know about you, but I’m going out to meet friends for a salad tonight!

Hope for hard-to-match kidney patients

The first (unsuccessful) human-to-human kidney transplant took place 75 years ago.  Some 16 years later, the first successful human transplant took place. Now, according to the United Network for Organ Sharing (UNOS), there are currently 111,714 people in the US awaiting organ transplantation.  Approximately 20,000 of these are so called “hard-to-match” kidney transplant patients.

In other words, their immune systems will reject most kidneys because of antibodies circulating in their blood that react to proteins known as human leukocyte antigens (HLA). These proteins are found on most cells and are used by the immune system to recognize what is foreign to the body.

In HLA-sensitized patients, the body has been exposed to foreign HLA in the past, either through pregnancy, blood transfusion or previous kidney transplant. As such, it immediately recognizes most donor organs as unfamiliar. And, unless these antibodies can be removed, they will result in severe antibody mediated rejection (AMR) and early loss of the transplanted organ.

Apart from the scarcity of donor kidneys, the biggest barrier to kidney transplant is the percentage (nearly 1:3) of patients on the waiting list whose immune systems make them likely to reject most kidneys available to them. Highly HLA-sensitized patients are very difficult to match with less than 7% receiving transplants each year.

SRxA’s Word on Health was therefore interested to hear of a new study from Johns Hopkins which showed that desensitizing such patients with a combination of therapeutic plasmapheresis and intravenous immunoglobulin (IVIG) doubled their chance of survival eight years after transplant surgery, as compared with those who stay on dialysis awaiting compatible organs.

Additionally, the protocol enabled a dramatic 98% transplant rate rather than the traditional 7%.

The results of this study should be a game changer for health care decision makers, including insurance companies, Medicare and transplant centers,” said lead investigator Robert A. Montgomery, M.D., D. Phil. “There’s a dramatic survival benefit, so people should take note. If this were a cancer drug that doubled chances of survival, people would be lined up out the door to get it. It’s really extraordinary to go from 30 percent survival to 80 percent survival after eight years.”

Widespread use of the pre-surgery protocol developed at Johns Hopkins could potentially lead to 3,000 more kidney transplants from living donors each year. The protocol uses plasmapheresis to remove the HLA from the blood before the transplant, then the patient receives low-dose intravenous immune globulin (a human plasma protein) to replace the problematic antibodies and prevent their return. This process is performed every other day for several days before transplant and then for up to 10 days following the surgery.

Although the protocol has great benefit in living donor transplants, it cannot be used in patients receiving cadaver organs – where time is of the essence,  because several days of plasmapheresis and IVIG are needed before surgery can take place.

Additionally, the patient will still to take the same anti-rejection drugs as all other organ transplantation patients.

The desensitization protocol also makes kidney transplants more expensive, However, the cost savings when compared to remaining on dialysis are enormous. Better still, the patient no longer has to endure the difficulties of dialysis, a process that takes about five hours a day, three days a week, and which often makes the tasks of daily life from working to caring for children nearly impossible.

“This treatment increases survival, ensures a better lifestyle and saves the health care system money,” says Montgomery. “There aren’t many things like that.”

Let’s hope healthcare insurers are reading this and taking note.

Uncontrolled asthma leads to out of control costs

SRxA’s Word on Health has often reported on the price of non-adherence to treatment . So, although we were shocked, we weren’t surprised to learn that poorly controlled asthma doubles costs and affects children’s performance in school.

According to a study just published in the Annals of Allergy, Asthma and Immunology  children with very poorly controlled asthma miss an average of 18 days from the classroom; whereas kids whose disease is better controlled, are absent for two days or less.

The investigators from National Jewish Hospital studied 628 children aged 6-12 with severe asthma. They looked at direct medical costs such as medications, unscheduled doctor visits, emergency department visits and hospital admissions as well as the indirect costs such as school days lost.

Patients were divided into three groups: very poorly controlled, not well controlled and well controlled. Costs were evaluated at the start of the study and then one and two years later.

The group, led by Stanley Szefler MD found that the costs for very poorly controlled patients were twice as high as those of the other groups at baseline. Very poorly controlled patients cost $7,846, compared with $3,526 for not-well controlled and $3,766 for well-controlled.

Two years later the costs for the very poorly controlled group had risen to $8,880 while costs for those with well-controlled asthma dropped to $1,861.  Indirect costs accounted for approximately half the total asthma costs for very poorly controlled asthma patients at each time point.

The authors concluded that very poorly controlled asthma is a major economic burden and improvement in asthma control and is associated with reducing cost.

SRxA together with our expert Allergy and Pulmonary Advisors  can help pharmaceutical companies promote better management strategies that may significantly reduce this burden of illness. For more information, contact us today.