20090507-3

Scientists are exploring faster approaches to making vaccines against the H1N1 virus. 

MIT Technology Review, May 6, 2009, by Emily Singer  —  Fears over the H1N1 virus circulating the globe have abated somewhat this week, as a growing number of mild cases suggest that the swine flu virus is not as deadly as initially feared. However, public-health officials caution against becoming too complacent, and the Centers for Disease Control (CDC), in Atlanta, and others are still taking steps to produce a vaccine: the flu season is just beginning in the Southern Hemisphere, where the virus could mutate to become more pathogenic. It’s also possible that the virus could prove much deadlier in a second wave around the world, as was the case for the 1918 flu, which ultimately killed millions.

The CDC is currently growing a seed stock of the H1N1 virus–the first step in making a vaccine. This stock will be distributed to vaccine manufacturers around the world, who will begin production of a vaccine once they’re given the go-ahead from the CDC. However, existing methods for making flu vaccines carry some disadvantages: they are relatively slow and require large amounts of the virus to be grown in chicken eggs. Due to limited production capacity and a limited egg supply, manufacturers would need to halt or decrease production of the seasonal flu vaccine. “This is a very inefficient system that requires a nine-month lead time,” says Ted Ross, a microbiologist at the University of Pittsburgh. “We need something more rapid with something like swine flu.”

Thanks to previous pandemic fears–largely from the avian flu, a much deadlier but less transmissible virus–alternative methods for making vaccines have received a significant boost in recent years. In 2006, for example, the U.S. Department of Health and Human Services awarded $1 billion in funding to a number of vaccine makers, including GlaxoSmithKline, Novartis, and MedImmune, to develop alternative production methods. Now, for the first time during an active pandemic, researchers and pharmaceutical companies are using these approaches to make vaccines against the current strain even before efforts have begun using traditional methods.

Novartis has already developed a vaccine for seasonal flu that is grown in cell culture, using methods similar to those employed to make biological drugs and other products; it has been approved for use in Europe. “The advantage is that cell culture can be expanded enormously,” says Andrea Gambotto, also at the University of Pittsburgh. “You can culture thousands of liters of cells, whereas there is a limited capacity to produce eggs.”The company is now using both cell-culture-based and egg-based technology to create an H1N1 vaccine. While the former is faster, cell-based manufacturing capacity is limited for this new approach, says a spokesperson for Novartis.

Despite the quick start, “it’s not clear that anything but the conventional technology will be in place in time to generate clinical vaccines that are going to be needed next year,” says Gary Nabel, director of the Vaccine Research Center at the National Institute for Allergy and Infectious Diseases (NIAID), in Baltimore. That’s because these new vaccines will need to undergo extensive animal and human testing before they can be marketed. (That process may move faster in the European Union, where cell-culture-based methods have already been approved for commercial use, than in the United States.) Still, the effort will not be wasted. Researchers see the latest flu scare as sort of a trial run for the next potential pandemic strain, which may be much more serious. “It’s more of a research exercise to see how quickly we can respond to a new strain of influenza,” says Gambotto.

Others are developing vaccines that use only portions of the virus, and are thus easier to grow in cells. (Intact viruses can sometimes be toxic to both eggs and cell culture.) Nabel and his collaborators at NIAID’s Vaccine Research Center are developing DNA-based vaccines, in which circular pieces of DNA containing the virus’s HA gene are grown in bacteria. Researchers have already developed an H5N1 vaccine using this technology; it is currently in human trials. “We could have a vaccine ready to go into clinical trials in two to three months,” says Nabel. “But whether that will elicit the same magnitude of response as a conventional vaccine, or whether we have to do something to enhance that response, we don’t know.”

Ross and others are taking another approach: developing viruslike particles. “We take a set of genes from the virus and use it to generate a particle that looks like a virus but isn’t able to replicate,” says Ross. “The immune system reacts to it, even more robustly than it reacts to a traditional vaccine.” The advantage of this approach is that a candidate vaccine can be generated as soon as the viral sequence is available. “The H1N1 sequences are already on the Internet, so you can generate a vaccine even without access to the virus itself,” says Ross. “We will have a vaccine to test in preclinical trials in a few weeks.”

Many unknowns will affect how vaccine production proceeds in the coming months. The CDC still hasn’t decided whether to begin production of an H1N1 vaccine soon, or whether to hold off and include the H1N1 strain in next year’s seasonal flu vaccine. “We’re already working to ramp up the production of the seasonal flu vaccine so that, should we decide to manufacture a vaccine for the H1N1, we’d be able to do that,” said Richard Besser, acting director of the CDC, at a press conference earlier this week.

“We’ll be working very closely with the international community to understand what happens to this virus over the next few months as flu season begins in the Southern Hemisphere,” said Besser. “That will tell us a lot about whether the virus is changing, whether it’s becoming more severe, and what measures we might want to take in the fall.” For example, if the virus does mutate to become more deadly, it’s not clear that a vaccine made against the circulating strain would protect against the new strain.

20090507-2

Press Release – Pan American Health Organization (regional office of WHO)

Expert says stigmatization of affected people and countries is unwarranted

Washington, D.C., May 6, 2009 (PAHO/WHO) – While the vast majority of confirmed cases of influenza A(H1N1) have been in the Northern Hemisphere, a top Pan American Health Organization (PAHO) expert today cautioned that Southern Hemisphere countries should remain on high alert, as their winter season is just now beginning. 

“There is a strong likelihood that there will be an upsurge of cases in your countries,” said Dr. Jon K. Andrus, PAHO’s lead senior technical advisor in immunizations. “Implementing your pandemic plans is very important. Most countries are already protecting their populations with seasonal vaccination as we speak. In addition, most, if not all, of our Southern Hemisphere countries have already enhanced their surveillance and monitoring procedures. The challenge will be not to drop your guard.”

North America (Mexico, the United States and Canada) currently accounts for all but 7 of the total 1,255 confirmed influenza A(H1N1) cases in the Americas. Three other countries in the PAHO region have reported the 7 additional cases: Colombia (1), Costa Rica (4), and El Salvador (2).

Andrus noted that the World Health Organization’s pandemic alert level could be raised from 5 to 6 if sustained community transmission of influenza A(H1N1) were to be found in another WHO region.

“In our region, most countries are already implementing their emergency plans,” said Andrus. “The term phase 6 is more relevant for the rest of the world than it is for us because we are already implementing our emergency plans.”

Andrus emphasized that PAHO and WHO are recommending that countries not impose travel restrictions nor close borders.

“We would also like to emphasize that countries around the world should be fair with individuals. It is not helpful to blame or stigmatize people who happen to be citizens of affected countries or happen to become victims of the disease.”

Andrus also described how Mexico is currently handling suspected cases of influenza A(H1N1).

First, providers decide whether a patient’s symptoms warrant a test for influenza A. If appropriate, treatment is provided. Next, depending upon the facility’s capabilities, the specimen is tested on site or sent to a reference laboratory for analysis. If the result is positive for influenza A, the patient is classified as a probable case, and the specimen is sent to a more specialized lab to determine if it is positive for influenza A(H1N1). If the result is positive, the case is considered confirmed.

Subsequent investigation focuses on when and where the patient may have been infected, and who else might have been exposed. Known contacts are notified and tested as well.

In addition, virologists study the virus’s genetic makeup to better understand it and determine how it may be mutating.

“I hope you can begin to imagine the huge volume of effort that all this work entails,” Andrus said. He added that PAHO, the Public Health Agency of Canada, and the U.S. Centers for Disease Control and Prevention (CDC) are assisting these efforts by mobilizing their own experts as well as others from countries throughout the hemisphere.

“We have never had such close surveillance of the emergence of a new virus such as for this new influenza A(H1N1) virus,” said Andrus, “and so we are learning as we go.”

PAHO, founded in 1902, works with all the countries of the Americas to improve the health and quality of life of their peoples. It also serves as the Regional Office for the Americas of the World Health Organization (WHO).
 

For more information please contact Daniel Epstein, Information Officer, Knowledge Management and Communication, tel (202) 974-3459, fax (202) 974-3143, or Donna Eberwine-Villagrán, Public Information Officer, Knowledge Management and Communication, tel (202) 974-3122, fax (202) 974-3143.

A shift in public perception about vaccine safety threatens the success of immunization programs.

Vaccines are one of the greatest advances in medical history. In just the past 50 years, polio, measles, rubella, mumps, and Haemophilus influenzae type B disease have nearly disappeared in the U.S. A group of experts has reviewed the history of immunizations in the U.S., the evidence that supports immunization requirements, and current threats to our successful immunization program. Their report includes the following:

  • In 1969, 17 states had laws that required immunization for school entry; by the early 1980s, all 50 states required immunization.
  • Rates of nonmedical exemptions (because of religious, philosophical, or personal beliefs) for required school immunizations increased from about 1% in 1991 to 1.5% to 2.5% in 2004. The exemption rate for religious reasons during this period remained at about 1%.
  • Concern about safety is the principal reason parents refuse immunizations.
  • Increasingly, parents are choosing to delay vaccination of their children or follow alternate vaccine schedules rather than schedules recommended by expert committees.
  • Unvaccinated children are significantly more likely to contract measles and pertussis than vaccinated children.
  • Compared with undervaccinated children, unvaccinated children are more likely to be white, live in higher-income households, and have a married mother with a college education.
  • Parents continue to report that healthcare providers are the most frequent source of information about immunizations.

The AAP Committee on Bioethics advises against discontinuing care for families that refuse vaccines, yet 40% of pediatricians report that they would no longer provide care to families who refuse all vaccines.

Comment: During the past 10 years, new vaccines have been introduced at a dizzying pace. Is vaccine fatigue – among both parents and physicians – affecting immunization rates? The childhood immunization schedule used to be relatively easy to follow. Now, three separate schedules exist, each with detailed comments (http://www.cispimmunize.org/IZSchedule_Childhood.pdf, http://www.cispimmunize.org/IZSchedule_Adolescent.pdf, and http://www.cispimmunize.org/IZSchedule_Catchup.pdf). Simultaneous increases in the number of immunizations and rates of autism and allergic diseases have fueled concerns about a link between these conditions and vaccines, despite no credible evidence of an association. The more knowledgeable we are about possible safety issues, the better we can address parental concerns (JW Pediatr Adolesc Med Jan 28 2009). As we move toward a more complicated adolescent vaccination schedule, further adherence issues will arise, particularly because most adolescents visit their primary care provider less than once each year. I can envision a time when immunizations will be required for high school graduation just as they are for school entry. In view of the shift in perception about the safety of vaccines, we must remind our patients – and ourselves – that immunizations are responsible for saving more lives than virtually any other medical advance.

Howard Bauchner, MD

Published in Journal Watch Pediatrics and Adolescent Medicine May 6, 2009

Citation(s):

Omer SB et al. Vaccine refusal, mandatory immunization, and the risks of vaccine-preventable diseases. N Engl J Med 2009 May 7; 360:1981.

May 6, 2009  —  The ongoing outbreak of novel influenza A (H1N1) continues to expand in the United States. CDC expects that more cases, more hospitalizations and more deaths from this outbreak will occur over the coming days and weeks.

CDC continues to take aggressive action to respond to the expanding outbreak. CDC’s response goals are to reduce spread and illness severity, and provide information to help health care providers, public health officials and the public address the challenges posed by this emergency.

CDC is issuing updated interim guidance daily in response to the rapidly evolving situation.

School Guidance

This includes updated interim guidance for schools and childcare facilities on preventing the spread of novel influenza A (H1N1) virus. At this time, CDC recommends the primary means to reduce spread of influenza in schools focus on early identification of ill students and staff, staying home when sick, and good cough etiquette and frequent hand washing. Decisions about school closure should be at the discretion of local authorities based on local considerations.

Increased Testing

CDC has developed a PCR diagnostic test kit to detect this novel H1N1 virus and has now distributed test kits to all states in the U.S. and Puerto Rico. The test kits are being shipped internationally as well. This will allow states and other countries to test for this new virus. This increase in testing capacity is likely to result in an increase in the number of reported confirmed cases in this country, which should provide a more accurate picture of the burden of disease in the United States.

U.S. Human Cases of H1N1 Flu Infection
(As of May 6, 2009, 11:00 AM ET)

States

# of
laboratory
confirmed
cases

Deaths

Alabama

4

 

Arizona

48

 

California

67

 

Colorado

17

 

Connecticut

4

 

Delaware

33

 

Florida

5

 

Georgia

3

 

Hawaii

3

 

Idaho

1

 

Illinois

122

 

Indiana

15

 

Iowa

1

 

Kansas

2

 

Kentucky*

2

 

Louisiana

7

 

Maine

1

 

Maryland

4

 

Massachusetts

45

 

Michigan

8

 

Minnesota

1

 

Missouri

2

 

Nebraska

4

 

Nevada

5

 

New Hampshire

2

 

New Jersey

7

 

New Mexico

3

 

New York

97

 

North Carolina

7

 

Ohio

5

 

Oklahoma

1

 

Oregon

15

 

Pennsylvania

1

 

Rhode Island

2

 

South Carolina

16

 

Tennessee

2

 

Texas

61

2

Utah

1

 

Virginia

3

 

Washington

9

 

Wisconsin

6

 

TOTAL (41)

642 cases

2 deaths

International Human Cases of Swine Flu Infection
See: World Health Organization

*Case is resident of KY but currently hospitalized in GA.

WHO UPDATE

WHO Panel Will Weigh Full-Scale Production of H1N1 Vaccine, May Halt Seasonal Vaccine Production

 

May 6, 2009 – The World Health Organization (WHO) will convene a panel of experts on May 14 to consider whether to initiate large-scale production of a vaccine for the swine-origin influenza A (H1N1) virus as well as whether to halt production of next fall’s seasonal flu vaccine, a WHO official announced today.

Marie-Paule Kieny, PhD, director of the Initiative for Vaccine Research at WHO, said during a press conference that any recommendation to stop making seasonal vaccine – which will allow manufacturers to switch over to H1N1 vaccine production much faster – will depend on how much of the seasonal vaccine has already been produced.

“We wouldn’t want to have no seasonal flu vaccine,” said Dr. Kieny. “I think we have quite a bit of produced.”

Another decision point is determining whether vaccinating against H1N1 influenza will require 1 or 2 doses. Seasonal vaccines require only 1 dose except in the case of small children who have never been exposed to seasonal flu, said Dr. Kieny. In contrast, planning for an avian influenza pandemic has assumed 2 doses of vaccine.

In the case of the new virus, Dr. Kieny said that 1 dose of the H1N1 vaccine may be adequate if exposure to the human influenza A (H1N1) virus has given adults some background immunity to the new virus. Researchers will find this out in clinical trials several months from now, she said.

WHO is meeting with manufacturers to ensure that supplies of any new H1N1 vaccine go to developing countries as well as developed ones, Dr. Kieny said, and noted that developed countries have contracted with vaccine makers to preorder pandemic vaccines. But manufacturers have such large capacity that even with larger orders already booked, they still should be able to make supplies available to poorer nations, Dr. Kieny explained.

WHO estimates that vaccine manufacturers worldwide are capable of making between 1 billion and 2 billion doses of an H1N1 vaccine.

As of 11:00 am EDT, 1658 lab-confirmed cases of infection with the swine-origin influenza A (H1N1) virus, and 30 deaths, have been reported in 23 countries.

20090507-1

A small satellite was launched last night to test antifungal drugs in orbit. 

MIT Technology Review, May 6, 2009, by Brittany Sauser  —  If you’re on the East Coast, you might be lucky enough to see a United States Air Force rocket sail through the air tonight, between 8:00 and 10:00 P.M. EDT, carrying a tiny satellite into space. Weighing in at a meager 10 pounds, the “nanosatellite,” called PharmSat, was developed by NASA to study how yeast responds to antifungal drugs while in orbit.

Past studies have shown that microorganisms can grow more virulent in space, and another nanosatellite mission, GeneSat, launched in 2006 to test how E. coli bacteria behave in space. The goal of such research is to better understand the biological effects of space. (GeneSat was an $8 million project, and its design is the basis for PharmSat.)

The new nanosatellite contains a sensor-studded laboratory that will detect the growth, density, and health of yeast cells receiving three different doses of the antifungal drug over the course of 96 hours. Scientists on the ground will initiate the experiment one hour after liftoff, and data will be sent back to Earth in near real time for up to six months, assuming that no technical glitches or failures occur.

MIT Technology Review, May 6, 2009   —  The U.S. biotech industry became profitable as a whole for the first time in 2008, a new report says, but the global financial crisis has led to a pullback in the investment that drives the industry’s expensive research.

Ernst & Young’s global biotechnology report 2009, its 23rd annual look at the industry said U.S. profit for the industry totaled $400 million. Globally, the still-developing industry lost $1.4 billion.

But young biotechnology companies are feeling the pinch from less venture capital as the financial crisis has quickly trickled down to them, the report said.

Meanwhile, the stock market declines of the past year have cut public investors’ appetite for risk — and biotech has always been a relatively risky neighborhood.

“It’s certainly difficult to see the public investors return the levels we’ve seen in recent years,” said Glen Giovannetti, Ernst & Young’s Global Biotechnology Leader.

Instead, many companies will have to start rethinking how they raise capital in a market where attracting investment is already highly competitive. More creative development partnerships or buyouts with long-term financial incentives could be one change. Also, innovation will count for a lot more as companies place their buyout bullseye on targets that have solid market prospects or development programs that mesh with their own plans.

“What we won’t see is just wholesale consolidation, gobbling up companies just because they are cheaper,” Giovannetti said.

In the latest report, Ernst & Young said the characteristics of the current financial crisis make it a threat unlike any other for the industry. Public capital is constrained, which in turn means less companies that go public through initial public offerings, while there is lower value in buyouts and less debt financing available.

Without funding, the long and expensive process of testing new drugs isn’t possible.

Still, ongoing trends such as the expansion of personalized medicine, a wave of generic drugs and the continued globalization of the sector should usher in more sustainable ways of financing drug development, according to the report.

Many key blockbuster drugs will soon face generic competition, which could remove some pricing demand facing the broader drug industry. The introduction of generic drugs could allow for better margins on truly innovative products, putting a premium on biotech, the report says.

“The movement to a system that measures and truly rewards companies based on the value their products deliver could give investors the returns they need and create the basis for a more sustainable business model,” the report said.

Despite the downturn, Giovannetti said, it’s not a “gloom and doom” situation for the sector, considering how necessary the many of the treatments are to a growing, and aging, population. In 2008, revenue at publicly traded biotech companies grew 12 percent $89.7 billion in 2008, while the global industry’s net loss improved to $1.4 billion from $3 billion, the report said.

Capital raised fell sharply, though, down 46 percent for the Americas and Europe combined to $16 billion. IPO funding all but disappeared, falling 95 percent to $116 million.