[ RadSafe ] News: RADIATION-KILLED BACTERIA VACCINE INDUCES BROAD IMMUNE RESPONSE IN MICE

[John Jacobus]

>From a list server I get. As noted:

"This advance is potentially of great importance in
meeting the challenge of creating vaccines that are
safe, effective and simple to manufacture and
transport," says NIH Director Elias A. Zerhouni, M.D.

---------------------
U.S. Department of Health and Human Services NATIONAL
INSTITUTES OF HEALTH NIH News National Institute of
Allergy and Infectious Diseases (NIAID)
http://www3.niaid.nih.gov/

EMBARGOED FOR RELEASE: Tuesday, July 25, 2006; 12:00
p.m. ET

CONTACT: Anne A. Oplinger, 301-402-1663,
aoplinger at niaid.nih.gov

RADIATION-KILLED BACTERIA VACCINE INDUCES BROAD IMMUNE
RESPONSE IN MICE

Vaccines made with bacteria killed by gamma
irradiation, rather than by standard methods of heat
or chemical inactivation, may be more effective, say
researchers supported by the National Institute of
Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health (NIH). Vaccines made
from gamma-irradiated bacteria also may not need to be
kept cold; an advantage in settings where
refrigerating vaccines is impractical or impossible. A
report on the research appears in the current issue of
the journal "Immunity".

In experiments with mice, scientists including Eyal
Raz, M.D., Sandip Datta, M.D., and Joshua Fierer,
M.D., of the University of California, San Diego,
School of Medicine demonstrated that a vaccine made
from irradiated "Listeria monocytogenes" bacteria,
unlike a vaccine made from heat-killed bacteria,
provides protection against challenge with live
Listeria. The irradiated bacteria also stimulated a
protective response from immune system cells called T
cells. Previously, only vaccines made from live,
weakened "Listeria" bacteria were believed capable of
eliciting a T-cell response.

"This advance is potentially of great importance in
meeting the challenge of creating vaccines that are
safe, effective and simple to manufacture and
transport," says NIH Director Elias A. Zerhouni, M.D.

Ideally, vaccines should stimulate a strong response
not only from both arms of the adaptive immune system
(antibodies and T cells), but also the body's innate
immune system. However, traditional ways of making
vaccines -- either by killing disease-causing agents
with heat, chemicals or by weakening (attenuating)
live pathogens -- have characteristic shortcomings.
For example, heat- and chemical-killed vaccines, while
safe and relatively easy to produce, generally produce
a less broad immune response than live, attenuated
vaccines. Conversely, it can be difficult to create
live, attenuated vaccines that safely preserve the
pathogen's ability to trigger strong innate and
adaptive immune responses.

"By showing that whole, irradiated bacteria can form
the basis of a vaccine that elicits a strong response
from both arms of the adaptive immune system, Dr. Raz
and his colleagues have opened the possibility of
making a variety of bacterial vaccines that combine
the best features of both killed-agent and live,
attenuated vaccines," says NIAID Director Anthony S.
Fauci, M.D.

Earlier research in Dr. Raz's laboratory had shown
that irradiated probiotics (bacteria that are
beneficial to health) retain the ability to trigger
innate immune system responses via proteins called
toll-like-receptors. Based on that observation, says
Dr. Raz, "we hypothesized that a vaccine made from
whole, irradiated bacteria would retain the properties
needed to evoke a broad immune response and result in
a superior vaccine compared with other methods of
killing the pathogen."

The investigators inactivated "Listeria" with lethal
doses of gamma radiation and then vaccinated a group
of 10 mice twice with the irradiated bacteria. Another
group of 10 mice received two inoculations with
heat-killed "Listeria", while a third group of 10
received no vaccine. Twenty-eight days after the first
vaccinations, all the mice were infected with a large
dose of live "Listeria" (four times the amount
required to kill 50 percent of infected unvaccinated
animals).
All the unvaccinated mice and all the mice vaccinated
with heat-killed "Listeria" died, but 80 percent of
the mice vaccinated with the irradiated bacteria
survived. Further experiments showed that protection
conferred by irradiated "Listeria" bacteria lasted for
at least 12 months, indicating that the vaccine
promoted the development of a "memory" T cell
response.

Consistent with their earlier experiments with
irradiated probiotics, Dr. Raz and his colleagues also
found that irradiated "Listeria"
retained the ability to stimulate innate immune
responses via toll-like-receptor proteins. "Although
completely inactivated by the radiation, and thus
unable to cause illness, irradiated bacterial
pathogens evidently retain characteristics that prompt
the immune system to mount a full-fledged defense,"
says Dr. Datta, the study's lead author. "In this
respect, irradiated pathogens more closely mimic the
body's response to a live, attenuated vaccine."

Finally, the scientists found that mice could be
protected by vaccination with irradiated "Listeria"
that had been freeze-dried into a powder. This point
is potentially of great practical importance, notes
Dr. Raz. A serious drawback of live, attenuated
vaccines is that they must be kept refrigerated at all
times: if the "cold chain" is broken, the vaccine is
liable to spoil and become useless. In countries with
reliable electricity, maintaining the cold chain is
rarely a problem.
The same is not true in less developed countries.
Vaccines made from whole, irradiated bacteria,
freeze-dried into an easy-to-transport powder, could
be reconstituted just before use, explains Dr. Raz,
thereby eliminating the cold chain requirement.

It is also possible that a strategy based on
irradiation-inactivated whole pathogens could rapidly
yield vaccines against such bacterial diseases as
typhoid, cholera, tuberculosis and other diseases of
public health concern, such as intestinal parasites.
This strategy might also be deployed in the event of
epidemic outbreaks or against bioterrorist attacks,
says Dr. Raz.

News releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at
http://www.niaid.nih.gov.

NIAID is a component of the National Institutes of
Health. NIAID supports basic and applied research to
prevent, diagnose and treat infectious diseases such
as HIV/AIDS and other sexually transmitted infections,
influenza, tuberculosis, malaria and illness from
potential agents of bioterrorism. NIAID also supports
research on basic immunology, transplantation and
immune-related disorders, including autoimmune
diseases, asthma and allergies. 

The National Institutes of Health (NIH) -- "The
Nation's Medical Research Agency" -- includes 27
Institutes and Centers and is a component of the U.S.
Department of Health and Human Services. It is the
primary federal agency for conducting and supporting
basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures
for both common and rare diseases. For more
information about NIH and its programs, visit
www.nih.gov.
  
##

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Reference:  D Rachmilewitz et al. Toll-like receptor 9
signaling mediates the anti-inflammatory effects of
probiotics in murine experimental colitis.
"Gastroenterology" 126:520-28 (2004).

SK Datta et al. Vaccination with irradiated "Listeria"
induced protective T cell immunity. "Immunity". DOI:
10.1016/j.immuni.2006.05.013 (2006).
--------------------------------------

This NIH News Release is available online at:
http://www.nih.gov/news/pr/jul2006/niaid-25.htm.

To subscribe (or unsubscribe) from this list, go to
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+++++++++++++++++++
>From the Slate:

Cheez Whiz In His Veins: Harry Olivieri, credited with co-inventing the 
Philly cheesesteak, died at 90. "My father is just as famous as the man 
who created the wheel," his daughter said, "except the wheel is a 
little less fattening and it won't end up on your hips."

-- John
John Jacobus, MS
Certified Health Physicist
e-mail:  crispy_bird at yahoo.com

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