|H9N2 Avian Flu Vaccine Paired with Adjuvant
Provokes Strong Human Immune Response at Low Doses
When combined with an immune-boosting substance called an adjuvant,
low doses of an experimental vaccine against a strain of avian
influenza (H9N2) provoked a strong antibody response in human volunteers,
report scientists supported by the National Institute of Allergy
and Infectious Diseases (NIAID), part of the National Institutes
The clinical trial of 96 adults was conducted at the NIAID-supported
Viral Respiratory Pathogens Research Unit at Baylor College of
Medicine, Houston, and was led by Robert L. Atmar, M.D. The results
are now online in Clinical Infectious Diseases.
“The results of this clinical trial add to the growing body of
information demonstrating the potential value of adjuvanted avian
influenza vaccines,” says NIAID Director Anthony S. Fauci, M.D.
An adjuvant is a substance that is added to a vaccine to boost
the body’s immune response to the vaccine’s antigen. “In the event
of an influenza pandemic, adjuvanted vaccines could provide a way
to extend a limited vaccine supply to more people,” he adds.
In 1999, two children in Hong Kong became infected with H9N2,
a strain of avian influenza that had not previously been detected
in humans. Humans have little or no natural immunity to a virus — such
as H9N2 or the more deadly H5N1 avian influenza — that historically
has circulated only in birds. If H9N2 or H5N1 were to acquire the
ability to spread easily from person to person, an influenza pandemic
could result, health experts say.
In 2004, NIAID directed Novartis Vaccines and Diagnostics (formerly
Chiron Corporation) to produce 40,000 doses of an experimental
H9N2 vaccine at its vaccine manufacturing facility in Siena, Italy.
Some of the vaccines were formulated with Novartis’s MF59 adjuvant.
Dr. Atmar and his colleagues tested the vaccines in volunteers
aged 18 to 34 in this Phase I clinical trial. Phase I vaccine trials
assess candidate vaccines’ safety and ability to stimulate an immune
response, and are not designed to determine whether the vaccine
would prevent infection by naturally occurring virus. The researchers
vaccinated 48 volunteers with non-adjuvanted H9N2 vaccine (made
from inactivated virus) at one of four dosages — 3.75, 7.5,
15 or 30 micrograms. An additional 48 volunteers received MF59-adjuvanted
vaccine at one of the same four dosages. Volunteers were vaccinated
twice, with inoculations spaced 28 days apart.
An avian flu vaccine, like the seasonal flu vaccine, should stimulate
antibodies, which help ward off infection if the vaccinated person
later encounters the flu virus. In general, the higher the level
of antibodies made in response to a vaccine, the more protective
the vaccine is, Dr. Atmar notes.
“In our trial, a single inoculation of adjuvant-containing H9N2
vaccine, even at the lowest dosage, generated a good antibody response,” says
Dr. Atmar. By comparison, the seasonal flu vaccine contains 15
micrograms each of three different circulating flu strains — much
higher than the 3.75 micrograms of H9N2 flu virus contained in
the lowest dose vaccine tested in this trial. Furthermore, he adds,
a single dose of the adjuvanted H9N2 vaccine was as good as two
doses of the vaccine without adjuvant.
Currently, MF59 is licensed for use as a vaccine adjuvant in Europe
but not in the United States. The results of this trial, says Dr.
Atmar, suggest that MF59 is deserving of further study.
For more information on influenza see http://www3.niaid.nih.gov/news/focuson/flu.
Also visit http://www.PandemicFlu.gov for
one-stop access to U.S. Government information on avian and pandemic
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.
News releases, fact sheets and other NIAID-related materials
are available on the NIAID Web site at http://www.niaid.nih.gov.
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
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