Scientists unlock mystery of potentially fatal reaction to smallpox vaccine

May 25, 2009

Researchers from the La Jolla Institute for Allergy & Immunology have pinpointed the cellular defect that increases the likelihood, among eczema sufferers, of developing eczema vaccinatum, a severe and potentially fatal reaction to the smallpox vaccine. The research, conducted in mouse models, was funded under a special research network created by the National Institutes of Health in 2004. The network is working toward the development of a new smallpox vaccine that could be administered to the millions of Americans who suffer from atopic dermatitis, a chronic, itchy skin condition commonly referred to as eczema.

The La Jolla Institute's Toshiaki and Yuko Kawakami, M.D.s, Ph.D.s., a husband and wife scientific team, led the research group which found that activity levels of Natural Killer (NK) cells played a pivotal role in the development of vaccinatum in the mice. The activity of the NK cells, which are disease fighting cells of the immune system, was significantly lower in the mice that developed eczema vaccinatum than in normal mice that also received the smallpox vaccine. This knowledge opens the door to one day developing therapies that could potentially boost NK cell activity in eczema sufferers.

"Since atopic affects as many as 17 percent of children in the U. S. and since eczema vaccinatum carries a fatality rate of 5-10 percent, therapies that prevent or treat eczema vaccinatum successfully are crucial should the need for mass vaccination against smallpox arise in response to bioterrorism," said Harvard pediatrics professor Raif S. Geha, M.D., chief of immunology at Boston Children's Hospital and a principal investigator in the NIH funded network investigating eczema vaccinatum. "The discovery of the Kawakami team, who are participants in the NIH network, is an important step towards this goal."

People with active atopic dermatitis (eczema), or who have outgrown atopic dermatitis, and the people they live with currently cannot receive smallpox vaccinations because of the risk of eczema vaccinatum. While uncommon, eczema vaccinatum can develop when atopic dermatitis patients are given the smallpox vaccine or come into close personal contact with people who recently received the vaccine. It is estimated that a significant portion of the U.S. population is currently not eligible for smallpox vaccination.

"This discovery answers an important question that has long eluded the scientific community, "why people with atopic dermatitis were susceptible to developing eczema vaccinatum upon receiving the smallpox vaccine, while the general population was not," said Mitchell Kronenberg, the La Jolla Institute's president & scientific director. "It marks a significant advance toward the goal of ensuring that everyone can one day be protected against the smallpox virus."

The finding was published today in the online version of the Journal of Experimental Medicine in a paper entitled, "Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum." La Jolla Institute scientist Shane Crotty, Ph.D., also contributed to the study.

Regarded as the deadliest disease ever known to man, smallpox was officially eradicated worldwide in 1980 and routine vaccinations against the disease ended in the U.S in 1972. However, bioterrorism concerns have arisen over recent years regarding the deliberate distribution of the smallpox virus, which might make smallpox vaccinations once again necessary. Such concerns led to the creation of the Atopic Dermatitis and Vaccinia Network (ADVN), a consortium of medical and research institutions nationwide developed by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The network, which provided grant funding for the Kawakami's studies under NIH contact N01-AI40030C, was launched in 2004 with the goal of developing a new smallpox vaccine that would be safe for atopic dermatitis sufferers. It includes three consortiums, involving data, clinical testing and animal studies, of which Drs. Kawakami and the La Jolla Institute are members.

The Animal Studies Consortium was created to establish animal models of atopic dermatitis and investigate their immune responses to vaccinia — the virus used in smallpox vaccine. Drs. Kawakami were invited to join the consortium due to their creation of a new, more effective atopic dermatitis mouse model in 2004.

In their study, Drs. Kawakami showed that eczema-infected mice had higher levels of IL-17 cells, which are known to inhibit NK cell activity. "This higher level of IL-17 cells slowed down the ability of the NK cells to kill the vaccinia virus," said Yuko Kawakami, noting people with atopic dermatitis are also known to have higher numbers of IL-17 producing cells. "This led to the development of eczema vaccinatum when these mice received the smallpox vaccine."

Drs. Kawakami tested their theory by stimulating more NK cell activity in the eczema-infected mice. The higher activity led to the elimination of the eczema vaccinatum infection. "We are very excited by these findings, " said Toshiaki Kawakami. "Developing a safer is the most important thing in this field."

Source: La Jolla Institute for and Immunology


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  • Ashy - May 25, 2009
    • Rank: 1 / 5 (1)
    Finally they admit deaths because of smallpox vaccination...
  • gopher65 - May 25, 2009
    • Rank: 1 / 5 (1)
    Uh... Ashy, where have you been been for the past, like, ever? Deaths caused by *any* vaccine have never been denied (even the safe ones can still cause an allergic reaction, if nothing else. But then, some people are allergic to common things like *sunlight* too. You can't protect everyone from everything all the time).

    When you're dealing with an extremely deadly disease like smallpox, measles, or mumps (all very deadly, before they were (essentially) wiped out in the developed world), the deaths caused by the vaccines are a tiny fraction of the deaths that would have occurred without the vaccines.

    If you think that vaccination deaths are denied, then you're spending waaaay too much time listening to anti-vax propaganda campaigns, and not enough time doing research for yourself.
  • Ashy - May 25, 2009
    • Rank: 1 / 5 (1)
    For many years medical men didn't admit vaccination death rate 0.8-1.7%. Measles and mumps is not very deadly if child healthy at all, this diseases was called "deadly" after vaccine inventions. The deaths caused by the vaccines less than deaths caused diseases _at_middle_ages_, but now we have water-supply, canalization, and good food.

    I did research in hospital, my child falled there after DPT vaccination. She almost dead but medics say it was coincidence. At our ward there were 7 children with vaccination post-effects and only 2 with other problems.
  • gopher65 - May 25, 2009
    • Rank: 1 / 5 (1)
    Measles and mumps have a huge childhood death rate. Have you never wondered why people use to need to have 12 kids per family, but at the same time the population remained virtually stagnant? It was because of those childhood diseases (and, of course, starvation brought on by them not knowing what pesticides were yet).

    I'd rather have a 1% death rate from all vaccinations combined than an 80% death rate from all those nasty diseases.

    And yes, of course, those unlucky 1% will have angry and sad parents.

    I also like the disdain that you put on the words "medical men";). How old are you planning to live? Do you know what the "natural" human lifespan is in the wild? 25-35 years. That's it. Those "medical men" and their hated science are why you're not already dead.
  • Ashy - May 26, 2009
    • Rank: 1 / 5 (1)
    No, it was because of total dysentery, hunger, mud, and shit at streets. At town child death rate was 8/10, at country child death rate was about 2/10 at productive years and 6/10 at hungry years. Citizens, kings and queens washed themself 1-3 times for all life. It from chronics of middle ages, various memoirs, ets.

    When they made water-supply and canalization child death rate decreased at 100-1000 times even in countries without vaccination. Without canalization we will have very big death rate anyway, with or without today's medicine and vaccines.

    As for me, my life could be very short because of infarcts. I'm 24 years old and 1 year ago I had my first infarct immediately after taking wrong but prescribed drugs. Without taking any drugs I'm very healthy.
  • thermodynamics - May 26, 2009
    • Rank: not rated yet
    Ashy: I am sorry that you had a problem with some sort of vaccination for your child. However, given your age, it is not likely it was a smallpox vaccination (which is what this article is about). The actual number for deaths from historical data related to smallpox vaccinations was approximately 1 to 2 per million (approximately 0.000198%).

    Considering that the smallpox virus killed approximately 30% of those contracting it, that is a good trade off.

    By quoting unsubstantiated numbers and linking vaccination to some conspiracy, people endanger both their children and the children of those that are around their children.

    Vaccinate your children! Save lives.
  • Ashy - May 27, 2009
    • Rank: 1 / 5 (1)
    > The actual number for deaths from historical data related to smallpox vaccinations was approximately 1 to 2 per million (approximately 0.000198%).

    Find and read this, please:
    Razzel P. "Edward Jenner's Cowpox Vaccine: The History of a Medical Myth."

    For many centuries medicals praise bloodletting, and I think in a century all people will know about vaccine madness and will regard today's vaccination like we regard bloodletting.

    I never will vaccinate my children because I want they'll grow strong and healthy.

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