Natl. Institutes of Health Reports Progress on Ebola Vaccine

NIH NEWS RELEASE

National Institutes of Health

National Institute of Allergy and Infectious Diseases

Novel Vaccine Protects Monkeys from Ebola Infection

Few viruses are more feared than Ebola virus, the deadly microbe that
periodically attacks African villages and kills up to 90 percent of
those it infects. Although other viral diseases claim more lives each
year, the ruthless efficiency and nightmarish symptoms of Ebola virus
make a vaccine against this killer an important goal of scientists.
Now, as described in the November 30 issue of Nature, a team of
researchers led by scientists from the National Institutes of Health
(NIH) has developed a novel vaccine that prevents Ebola virus
infection in monkeys. All four vaccinated monkeys were completely
protected from a lethal dose of the virus. This study describes the
first primate model of immune protection against Ebola virus, a model
that may allow scientists to rationally design a vaccine that prevents
this dreaded disease in humans.

"Doctors have essentially been helpless against Ebola virus," says
Gary Nabel, M.D., Ph.D., director of the Dale and Betty Bumpers
Vaccine Research Center (VRC) at the NIH and a lead author of the
study. "We have not known if immunity to the virus exists or what
parts of the immune response are important. Our studies show that
animals can launch an effective immune response against Ebola virus,
and we can use knowledge of this response to design a vaccine that
protects non-human primates from infection. Although much more work
needs to be done, we hope this moves us closer to new vaccines and
treatments for Ebola and other viruses."

Ebola virus kills quickly, giving the body little time to launch an
effective immune response. Infected individuals suffer severe pain,
high fever and extensive internal bleeding. Although the virus
periodically strikes humans, scientists do not know where it resides
in nature between outbreaks.

"Ebola is a difficult virus because currently available antiviral
drugs have no proven effect on it and we do not know its natural
reservoir, making environmental control impossible. A vaccine is
therefore the best hope for protecting humans from infection, and this
study makes some key advances toward realizing that goal," says
Anthony S. Fauci, M.D., director of the National Institute of Allergy
and Infectious Diseases (NIAID), which funds the VRC along with the
National Cancer Institute (NCI). NIAID, NCI and the NIH Office of AIDS
Research spearhead the Center.

Dr. Nabel and colleagues had previously tested genetic Ebola vaccines
-- strands of DNA containing genes that encode Ebola virus proteins --
for their ability to induce immune responses in rodents and to protect
against disease. Unlike traditional vaccines, typically made from
viral proteins, DNA vaccines more closely mimic virus infection
because they enter a cell and use that cell's machinery to manufacture
new viral proteins. Researchers believe this strategy might better
trick the immune system into thinking a real virus infection has
occurred.

Previously, Dr. Nabel's laboratory and a second research team
independently showed a DNA vaccine could protect mice and guinea pigs
from a specially adapted Ebola virus strain lethal to rodents. An
effective human vaccine, however, must protect against three known
fatal Ebola virus strains - Zaire, Sudan and Ivory Coast. Ebola Zaire
is the form of virus associated with the most human deaths.

To ensure that a multi-strain vaccine would not weaken the immune
response to the Zaire strain, a team of scientists led by VRC research
fellow Nancy Sullivan, Ph.D., and Dr. Nabel combined genes encoding
surface proteins from the Sudan, Zaire and Ivory Coast Ebola viruses.
Working with researchers from the Centers for Disease Control and
Prevention's high-containment or biosafety level 4 facility, Dr.
Nabel's team compared this vaccine to the one tested previously in
rodents. The new vaccine produced an immune response equally powerful
to that of the original vaccine in protecting guinea pigs from the
Zaire strain.

The scientists then turned to boosting the anti-Ebola virus immune
response by using a weakened form of a different virus, adenovirus, to
make an Ebola virus protein from the Zaire strain. Adenoviruses
typically cause respiratory diseases, but the researchers used a
modified form that can enter cells without reproducing or causing
disease. Such viruses have been used in other studies to boost immune
responses in mice. Dr. Nabel's team attached the Ebola Zaire virus
surface protein gene to the DNA of the weakened adenovirus, and tested
this new booster vaccine in mice. The vaccine produced a more vigorous
immune response than that observed with the multi-strain DNA vaccine,
and it increased the amount of antibodies and T cells directed against
the Ebola virus protein.

Armed with this promising new vaccine, the researchers tested a novel
prime-boost immunization strategy on eight monkeys. Four monkeys
received the three-strain Ebola virus DNA vaccine and then were
injected with the Ebola-adenovirus booster. The other four monkeys
received placebo immunizations. All four vaccinated monkeys launched
strong anti-Ebola immune responses and survived a subsequent exposure
to lethal doses of Ebola Zaire virus. Three of these monkeys showed no
sign of viral infection, whereas a slight, temporary increase in Ebola
virus in the blood of one of the vaccinated monkeys disappeared after
one week. More than six months after infection, the four monkeys
remained symptom-free with no detectable virus in the blood.

The researchers are continuing their efforts. "We of course want to
test the multivalent vaccine for effectiveness against all three
strains of Ebola virus," says Dr. Sullivan, "but we also need to look
more closely at the immune response induced by these vaccines so we
can nail down what is needed for protection." By studying the
mechanism of protection induced by the vaccine, they can determine
what combination of antibodies, helper T cells and killer T cells
defend the monkeys against infection. They then hope to use this
information to rationally design new vaccines and antiviral treatments
for humans.

NIAID is a component of the National Institutes of Health (NIH). NIAID
supports basic and applied research to prevent, diagnose, and treat
infectious and immune-mediated illnesses, including HIV/AIDS and other
sexually transmitted diseases, tuberculosis, malaria, autoimmune
disorders, asthma axed allergies.