Malaria vaccine trial disappoints

[Islander]

By Maggie Fox
Wed Sep 29, 2010

WASHINGTON (Reuters) - The numbers were so bad that Dr. Stephen Hoffman did not even want to say them out loud.
"It was a low number," he said. Pressed, he added, "Only a handful." Finally he squeezed the numbers out. "We had five."
Out of 80 volunteers vaccinated with Sanaria's experimental malaria vaccine, only five were protected from infection in the company's first clinical trial.
The Maryland-based company, which opened its doors in 2007, has not given up. But its disappointing results illustrate the uphill battle to develop a vaccine against an infection that kills 800,000 people a year, most of them young African children.
Hoffman gave details about what his team of scientists learned from the trial at a conference of malaria vaccine makers and their backers being held in Washington this week.

Tests in animals suggest that perhaps giving the vaccine intravenously might provide better protection, and Hoffman, founder and chief executive of the small, privately held company, is planning ways to test the idea in people.
"The vaccine was used to immunize 80 volunteers and it was safe and well tolerated," he said in an interview. It did, as expected, stimulate an immune response against the malaria parasite - just not nearly as much as Hoffman had hoped.
Now Sanaria has run out of money from the non-profit PATH Malaria Vaccine Initiative. But Hoffman plans to continue with cash from the U.S. National Institutes of Health and perhaps other government agencies.
"Right now I do need to get a lot more funds," he said.

A malaria vaccine has been the dream of hundreds of experts but has been maddeningly hard to actually develop.
Malaria is caused by a parasite, and making a vaccine against parasites is much harder to do than vaccinating against one-celled organisms like bacteria, or the even simpler viruses.
Plus malaria, which is spread by mosquitoes, has a complicated life cycle, passing from the blood to the liver to other organs.

GETTING CLOSE
GlaxoSmithKline is testing what most experts consider the most promising malaria vaccine, one called RTS,S or Mosquirix.
"We're getting close - we are getting very close," Glaxo's Dr. Joe Cohen said in an interview.
Investigators in seven African countries have enrolled 12,000 children and need just 4,000 more. The first data on safety and efficacy are expected by the end of next year.
In earlier trials, the vaccine appeared to produce a good immune response in African children.
But the goal is set very low - the Malaria Vaccine Initiative is asking only for it to protect 50 percent of the children against severe disease for a year.

"We are looking into the possibility of a next-generation," vaccine," said Cohen. Glaxo has spent about $300 million on Mosquirix, plans to spend about another $100 million and will receive an additional $100 million or so from the non-profit Bill & Melinda Gates Foundation, for a total of $500 million.
Investigators at the conference swapped notes on Tuesday and Wednesday about what the trials have told them so far about trying to vaccinate against the Plasmodium falciparum parasite, which causes most cases of malaria.
And groups presented ideas for new ways to deliver vaccines - such as Pennsylvania-based Inovio Biomedical Corp, which is using its so-called electroporation delivery-DNA vaccine approach to try to make a vaccine against malaria, as well as flu and AIDS vaccines.

Electroporation involves making tiny holes in the skin instead of using a needle to deliver a vaccine.
Dutch biotechnology company Crucell has technology that uses a common cold virus called an adenovirus that can "prime" the immune system and may help get a better response to Glaxo's Mosquirix. Crucell has teamed up with Glaxo to test the two together.
Johnson & Johnson, which already owns nearly 18 percent of Crucell, said this month it planned to buy the Dutch vaccine maker for $2.3 billion.
Then there is the next goal, said Cohen - a vaccine against Plasmodium vivax, the parasite that causes most cases of malaria in Asia.

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[Maurya]

Concerning this one and the herpes one, as well, would this be a good chance for someone (perhaps Mellowsong or Reesacat or EmmaPeel) to expound on the differences between vaccination and immunization? These terms often are used interchangeably, and I understand somewhat of the difference. I have heard various experts on radio programs explain why an immune response does not necessarily mean that the person, or animal, has an actual resistance to the disease in question. Time for a review of these essential parameters? Someone smarter than me, please weigh in...

[mellowsong]

I'm not sure I'm answering what you are asking but:

Immunization is simply the process by which the human body gets prepared to attack an infectious micro-organism. Immunization occurs 2 ways: Active and Passive.

Active immunization occurs when an infectious agent enters the body and the body makes antibodies against it. Active immunization occurs naturally, such as catching a bug and then developing immunity against it (ie, the hundreds of cold viruses are good examples, once you have a particular one, you rarely get infected by the same virus again) . Active immunization also occurs through vaccination because the infectious agent is being introduced into the body and the body itself responds with antibodies.

Passive immunization occurs when the antibodies themselves are introduced into the body. One example of this is the passage of antibodies from mother to fetus. Another example of passive immunization is the administration of gamma globullins.

So, all vaccinations are immunizations but not all immunization is a vaccination.

The immune response occurs at the cellular level. If the cells responsible for mounting an attack are faulty, then the immune response will be faulty. Antibodies are basically keys that fit into the keyhole of the invader. If there is faulty production, the key may not fit just right. There are so many components that is it almost impossible to explain. You can develop antibodies that do little/no good due to a fault in the antibody itself, a minute mutation of the invading organism, insufficient production of antibodies and an overactive immune system that keeps the body in constant overdrive. The immune system protects not only against infectious invaders but anything it deems dangerous. An out of control immune system decides the body itself is dangerous (auto immune diseases) and produces antibodies against itself. People with autoimmune diseases and extreme allergies generally have poor defense against infectious agents. I'm probably oversimplifying here but trying to explain why merely the presence of antibodies does not indicate protection.

[Maurya]

Thanks, Mellowsong. That is exactly the information that I needed. I was unclear about the cellular mechanisms, and still will need to research some more to clarify some things in my thick head.