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August 10th, 2010
03:14 PM ET

NIH begins testing dengue vaccine

The National Institutes of Health has begun human clinical testing for a vaccine to prevent dengue infection, according to a news release.

The illness is acquired through the bite of certain species of mosquitoes, primarily Aedes aegypti, but also Aedes albopictus. Around the world, about 2.5 billion people live in areas where they are at risk.

The mosquitoes are also present in Florida, according to the Centers for Disease Control and Prevention.  And recently, the Florida Department of Health confirmed an increase in cases of dengue fever acquired in the Key West area with a count of 24, as of mid-July. Also 49 cases of “imported” dengue fever have been reported in Florida, involving people who’ve traveled to areas under a dengue endemic, such as the Caribbean or Central and South America.

CNN: Florida confirms 24 cases of dengue fever in Key West

The NIH has been developing a vaccine for more than a decade, according to the news release. Dengue infection can range from mild symptoms to severe hemorrhagic fever or shock syndrome, causing coma or death.

'Indescribable, crazy pain': Surviving dengue fever

The vaccine is undergoing clinical study at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. Designed by scientists at the National Institute of Allergy and Infectious Diseases, the vaccine is to protect against all four dengue viruses, ENV-1, DENV-2, DENV-3 and DENV-4, which are transmitted to humans by mosquitoes. The early clinical trials will test the vaccine’s safety and ability to stimulate immune responses.


soundoff (32 Responses)
  1. stillin

    so who do they test it on, exactly how do they test it, people? animals? why don't you explain it. It would be good to know exactly how the testing is done.

    August 10, 2010 at 19:11 | Report abuse | Reply
    • Please Read

      The first line in the article states that they have started a "human clinical testing", which means they will be testing HUMANS in a CLINICAL setting. It also provides a DIRECT LINK to the NIH's press release. And that the vaccine has been in the works for more than a decade.
      Oh dang you CNN, for not providing verbatum the press release in your article! Shame on you for expecting people to actually read a complete sentence and move the mouse to click on a link for the exact information they are requesting!! How will we ever find out beneficial information?!?!

      August 11, 2010 at 00:16 | Report abuse |
    • Claudia

      I am glad someone is working on something for this.

      Dengue Fever KILLED my mother last year 11/2009 when she traveled to Mexico. There is an outbreak in that country and nothing was done to warn our US citizens that travel there. No one takes things serious until it happens to one of your family members. Who would have thought something that small can do so much harm. My mother suffered a lot, we didn’t even get to say goodbye. We always wonder if she even knew what hit her. We brought her back to the U.S. but nothing helped save her life. Now we are alone and hart broken, we miss her. Since then we have research more on Dengue Fever. There are different types of it and unfortunately my mother had the worse the one that makes your internal organs fail and bleed. We also know that if you survive Dengue Fever once the second time its mortal. So people don’t take it for granted a little insect (mosquito) can kill you.

      August 18, 2010 at 08:24 | Report abuse |
  2. Claudia

    But Stillin, that would require them actually doing WORK and providing us with beneficial information.

    August 10, 2010 at 19:15 | Report abuse | Reply
  3. Elizabeth

    I'm really surprised they found a way to make the vaccine work for all four serotypes of the virus. Reinfection with a second serotype is what scientists think causes Dengue hemorragic fever, and initailly they couldn't include the four serotypes in a vaccine because the immunity from one caused a bad reaction when a second serotype was introduced. I"m very curious to read more about this vaccine! Good work science!

    August 10, 2010 at 22:59 | Report abuse | Reply
    • Please Read

      Again, answers to questions can be found, simply by taking the mouse and clicking the link. From the article

      "The new vaccine is tetravalent, meaning that it is designed to protect against all four dengue viruses, also called serotypes. This is especially important because of the way the immune system responds. A person who develops antibodies against one serotype of dengue virus is protected against only that specific serotype. To be fully protected against the four forms of dengue, a person must have antibodies against all four serotypes of the virus. However, having some antibodies to dengue may be worse than having none: Someone who has antibodies against only one or a few of the virus serotypes is actually at higher risk of developing the severe form of the disease upon infection by another serotype. But a person who is immune to all four serotypes cannot be reinfected, and, therefore, is less likely to develop DHF/DSS."

      By vaccinating for all four at the same time, you prevent the reaction from the second exposure from ever occuring.

      August 11, 2010 at 00:22 | Report abuse |
    • Elizabeth

      In a response to Please Read: When I was assisting with Dengue vaccine research 10 years ago the problem was that the tetravalent vaccine was causing a hemorragic reaction by introducing all the serotypes at the same time. The tetravalency was the problem, because as the immune system built protection against one, it would target the other three serotypes and cause a hemorragic fever like reaction. In essence, the one shot of vaccine counts as four different exposures. It doesn't mention how they got around this problem, and I'm very curious to know.

      August 11, 2010 at 06:09 | Report abuse |
    • Please Read

      In the article it stated that the first phase of the testing was to determine which monovalent vaccines gave the best response. They tested seven different ones for the four serotypes. In this phase II trial they are testing the seven different monovalent ones in combination to see which offers the best protection.

      I have never heard of anyone having building seperate immune responses to a vaccine at different times. The body doesnt work like that. If they were given the vaccine at one time, they would start making antibodies to simutaneously, not in sequential order to serotypes. I dont understand what you are saying here – the body wouldnt build a response to just one and then the others. It would respond to all at the same time. Unless the patient had prior exposure OR if they were just having a bad immune response all together.

      August 11, 2010 at 07:16 | Report abuse |
    • Please Read

      In addition, the vaccine is attenuated, so it cant cause disease anyway.

      August 11, 2010 at 07:27 | Report abuse |
    • MicroBio

      It is possible for an attenuated vaccine to still cause disease. Attenuated just means it is made less virulent, but the virus is definitely still viable.

      The initial issues with the tetravalent Dengue vaccines is what Elizabeth stated. While the body does develop antibodies to all 4 serotypes in the vaccine, the resposne is not equal. For example, there may be an overwhelming antibody response to Denv-1 but only sub-neutralizing antibodies to Denv-2,3,4. Researchers think that there is actual competition between the 4 viruses. To overcome this, they give booster shots, use different amounts of each serotype in the vaccine, etc

      For the record, because I know questions will come...I am a researcher working on a tetravlent Dengue vaccine using a mechanism completely different from what is in this article.

      August 11, 2010 at 13:08 | Report abuse |
    • Please Read

      Let me rephrase: it is EXTREMELY unlikely to cause disease, especially because it requires a secondary mutation. And in any case that could not be what they saw in what Elizabeth was describing, even if there was an adverse immune response after subsequent injections.

      So basically what you are saying was that earlier versions were not efficacious enough to produce a satisfactory response for some of the types. Then there is the answer as to what changed!

      August 11, 2010 at 13:33 | Report abuse |
    • Tom

      Good observation, Elizabeth. I worry that there could be a problem if a 5th or 6th variant shows up. Then we would have a population of vaccinees that may be at risk for hemorrhagic fever.

      August 11, 2010 at 15:30 | Report abuse |
  4. Nick

    Please Read: You're an ass.

    August 11, 2010 at 09:00 | Report abuse | Reply
  5. Please Read

    Yes Nick, I am the ass. Forgive me for having reading comprehension skills.

    August 11, 2010 at 09:19 | Report abuse | Reply
    • Nick

      Are you a condescending prick all the time or only when you can hide behind the anonymity of internet chat boards?

      August 11, 2010 at 10:28 | Report abuse |
    • Steph

      HAHA! Good one Nick. He is probably some fat middle-aged nerd who lives in his mother's basement and sleeps with dolls. LOSERRRRRRR.

      August 11, 2010 at 12:15 | Report abuse |
    • Please Read

      Actually, I am female and work in the pharmaceutical industry. And I am under 30. And can read at least at a high school level.

      August 11, 2010 at 12:42 | Report abuse |
  6. Elizabeth

    Another response: The problem researchers were encountering before, both with serial introduction of monovalent vaccines and with the tetravalent vaccines of the time, was, for example, DEN-1 serotype vaccine antibodies reacting to the presence of the DEN-4 serotype vaccine. It didn't matter when the second, third and fourth serotypes were introduced to the system, the simple presence of other serotypes was problematic. And of course an attenuated vaccine won't cause the actual disease, but you still get an immune response. Another challenge researchers were facing when developing the monovalent vaccines was balancing the efficacy of the attenuation, while still managing to confer a sufficient immune response. In many cases, the introduction of a monovalent vaccine would cause more problems later when the subjects were introduced to a different serotype than the one they had been innoculated against. Choosing the 4 most effictive monovalent vaccines and mixing them together sounds like a good idea, but I'm interested to know the practical details as that plan didn't work before. Reading the press release has simply whet my appetite for the hopefully soon to be published journal articles.

    August 11, 2010 at 10:45 | Report abuse | Reply
  7. Please Read

    Elizabeth, I think that they are trying to avoid the serial introduction, from my understanding anyway. Thats why they are all present at once in the vaccine. When you introduce them all at once, you develop antibodies to them at the same time – and thats why you are prevented from getting the disease regardless of what serotype you are introduced to at a later date. And in this case, the immune response is desired.

    Nick, I am only condenscending when the initial response to an article is automatically to denounce the writer for not "working" or "explaining" it to the reader. All the information is there. I find it more asenine to start degrading a writer for not providing adequate information instead of actually taking the time to read it. Especially when it is already provided. Whats your excuse?

    August 11, 2010 at 10:54 | Report abuse | Reply
    • Valerie

      "When you introduce them all at once, you develop antibodies to them at the same time"

      By this logic, we should combine all vaccines into one super vaccine. CNN just published with an article about the rate of febrile seizures increasing in people who take the MMR+V vaccine over the MMR vaccine. Perhaps immune response can be overwhelmed.

      August 11, 2010 at 11:18 | Report abuse |
    • Elizabeth

      I think the problem with the original tetravalent vaccines was that the four serotypes didn't confer equal immunity even when introduced at the same time, so people were getting infected by one of the strains of the virus via mosquito bite after being innoculated and therefore having a more severe response than they would have had they not been immunized. I would hope that the monovalent vaccines had become more efficacious over the course of time, and are now able to actually confer immunity with a greater rate of success. If this is the case, the main problem would be ensuring equal immunity from all four serotypes in the tetravalent vaccine. If they've moved on to human trials they must be well pleased with their initial animal study success rates.

      August 11, 2010 at 11:48 | Report abuse |
    • Please Read

      Valerie, many vaccines are multivalent. The HPV vaccine for example. Menig vaccines have components from 13 serotypes. You offer vaccines in combination not to cram as much as you can in one vaccine, but to confer immunity in a specific way. As Elizabeth mentioned, when you immunize against only one type, you can become more ill if you are infected with a type that is different than the one you were vaccinated against. In oder to have good protection, you have to be vaccinated against all of the types that cause the disease.

      August 11, 2010 at 12:50 | Report abuse |
  8. Chrles

    Thanks Please Read for the good info- ignore the hecklers.

    August 11, 2010 at 12:30 | Report abuse | Reply
  9. Joe

    This vaccine has been in the works for a very long time, and has still shown only modest ability to safely and effectively prevent recurrent dengue infection. It should also be mentioned that this is NOT an attenuated Dengue viral vaccine, this is a recombinant protein that has been formed in a virus and then attenuated, the report contradicts itself, since there are no known dengue viral vectors that are tetravalent, so it is a man-mad construct. The protein is made up of 4 of the 7 monovalent recombinant envelope proteins that have been made against Dengue. They then assembled this into 3 structurally variable models and will try and determine which of those is the safest/most effective. Overall, this is a poorly written press release with very sketchy scientific information being provided. Obviously due to the attempt at making it leyman.

    August 11, 2010 at 13:44 | Report abuse | Reply
    • Please Read

      I actually was confused by this too. It is recombinant then? I dont know how the NIH could make that mistake!

      August 11, 2010 at 15:15 | Report abuse |
    • MicroBio

      In the NIH report, they mention a man by the name of Stephen Whitehead. I know that he has had several publications that use attenuated viruses. They have used at least 3 different methods to attenuate, so I'm not sure which one is being tested. Joe, here is a link that was in the NIH report...all the vaccines are live attenuated http://clinicaltrials.gov/ct2/show/NCT01072786?term=dengue&state1=NA:US:MD&rank=11

      Also, a vector isn't necessarily needed for a tetravalent Dengue vaccine. There are some researchers that use alpha virus or lentil viral vectors to deliver a vaccine, but I don't think this is the case here. Usually tetravalent dengue vaccines consist of a mixture of 4 monovalent vaccines. So for one tetravalent that they are testing, the vaccine consists of 10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3-3´D4Δ30, 10^3 PFU of rDEN4Δ30-200,201.

      August 11, 2010 at 16:52 | Report abuse |
    • Joe

      Hi MicroBio,

      You are correct. Which gives me even greater pause as to the broad range efficacy of this method. Live attenuation viral vaccinations are inherently more complex. Given vast epidemiological differences across many races and indigenous locations, it is alarming to me to use attenuated virus as the vaccines, especially in a compounding infection disease like Dengue. As always I will be interested to see how this turns out, though this reminds me of the recent article I read about the attempted HIV vaccinations that are being explored at the moment.

      However, It's not really "tetravalent" if it's just a mixture of 4 monovalent vaccines. This was the cause for my misunderstanding. Valency indicates a connection or bond. In actuality, these are just mixtures. There are true tetravalent recombinant vaccines under investigation for Dengue vaccination, 1 protein, 4 discrete immunogenic regions.

      August 12, 2010 at 08:45 | Report abuse |
  10. Enrique Romero

    Elizabeth, ¨Please Read¨, and others: I am definitely interested in this subject. I´m a General Practitioner in Honduras, where dengue is definitely front page news right now, with 2-3 deaths daily due to dengue. Could you please send any info or comments or links to enriqueromerol@lgmail.com ?

    August 11, 2010 at 14:45 | Report abuse | Reply
  11. Enrique Romero

    PS- you will probably wonder why I don´t get the facts from medical publications. Answer: 1.) subscriptions cost money- dollars-(doctor in Thirld World environments don´t earn all that much! – 2.) you sound as if you have interesting inside info.

    August 11, 2010 at 14:48 | Report abuse | Reply
  12. KJ

    I had dengue fever when I lived in Nicaragua, it was pretty nasty. They said to be careful of getting a second time because it is often much worse that the first. Hence the different strains of Dengue causing more severe reactions after the first infection because of the immune systems response I take it...very interesting. I hope they do intvent a vaccine, I wouldn't wish dengue fever on my worst enemy 🙁

    August 11, 2010 at 15:08 | Report abuse | Reply
  13. Arlier Dismukesf

    Sketches are in fact nice source of teaching instead of wording, its my know-how, what would you say?

    July 30, 2012 at 00:03 | Report abuse | Reply
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