|H5N1 Avian Flu Virus Vaccine Induces Immune Responses in Healthy
Results from a clinical trial demonstrate that high doses of an experimental
H5N1 avian influenza vaccine can induce immune responses in healthy adults. Approximately
half of those volunteers who received an initial and a booster dose of the highest
dosage of the vaccine tested in the trial developed levels of infection-fighting
antibodies that current tests predict would neutralize the virus. The National
Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes
of Health, funded the study, published in the current issue of The New England
Journal of Medicine. Preliminary results from this trial were first disclosed
late last summer.
“These findings represent an important step forward in the nation’s efforts
to prepare for the possible emergence of a human pandemic of H5N1 avian influenza,” notes
NIH Director Elias A. Zerhouni, M.D.
“We are working hard to address the many challenges that remain with regard
to the development of an H5N1 vaccine,” adds NIAID Director Anthony S. Fauci,
M.D. “For example, potentially protective immune responses were seen most frequently
at the highest dose of this vaccine. We are investigating other options that
may allow us to reduce the dosage — for example, adding an immune booster,
or adjuvant, to the vaccine — so we can achieve a more practical immunization
strategy.” In addition, the U.S. Department of Health and Human Services is pursuing
other approaches to an H5N1 vaccine, including vaccines made in cell cultures
rather than grown in eggs.
H5N1 avian influenza viruses are of enormous concern to public health officials
worldwide. The potential for a human avian flu pandemic looms large, say experts,
as daily reports indicate an increasing spread of infection in bird populations
in Southeast Asia, Europe, the Middle East and Africa. According to the World
Health Organization, as of March 24, 2006, 186 people had been infected with
avian flu viruses, and more than half of them had died.
Generally, flu viruses are easily transmitted from person to person, but so
far, the H5N1 avian influenza viruses have not demonstrated this characteristic.
In the worst-case scenario, if an avian flu virus became easily transmissible
from person to person, it could trigger an influenza pandemic because humans
have no pre-existing immunity to these viruses.
The trial, conducted between March and July 2005, was carried out at three NIAID-supported
Vaccine and Treatment Evaluation Units located at the University of Rochester
Medical Center in Rochester, NY; the University of Maryland School of Medicine
Center for Vaccine Development in Baltimore; and the Los Angeles Biomedical Research
Institute at Harbor–University of California Los Angeles Medical Center. John
Treanor, M.D., of the University of Rochester, led the group.
The study was conducted in two stages. In the first stage, the research team
enrolled 118 healthy adults ages 18 to 64 years old. Each participant was assigned
at random to one of five groups. Volunteers in each group received an initial
dose of vaccine (7.5 micrograms [mcg], 15 mcg, 45 mcg or 90 mcg) or saline placebo
into the upper arm muscle; about one month later, they received a booster shot
of the same vaccine dosage or the placebo. The research team collected blood
samples before each vaccination and one month after the second vaccination.
Before the study could be expanded, an independent Data and Safety Monitoring
Board assessed the vaccine’s safety by reviewing data collected through day 7
after the second vaccination; no safety concerns were found. The investigators
then began stage two of the study, eventually enrolling an additional 333 healthy
adult volunteers into the trial according to the same protocol design as in stage
The NEJM article describes an analysis of data on the safety and immune
responses to the vaccine. In general, the higher the dosage of vaccine, the greater
the antibody response produced. Of the 99 people evaluated in the 90-mcg, high-dose
group, 54 percent achieved a neutralizing antibody response to the vaccine at
serum dilutions of 1:40 or greater, whereas only 22 percent of the 100 people
evaluated who received the 15-mcg dose developed a similar response to the vaccine.
Generally, all dosages of the vaccine appeared to be well tolerated:
- Almost all reported side effects were mild
- The second dose of vaccine did not cause more local or systemic symptoms
than the first
- Systemic complaints of fever, malaise, muscle aches, headaches and nausea
occurred with the same frequency in all dosage groups as in the placebo group
- Lab tests did not reveal any clinically significant abnormalities
The vaccine, made from an inactivated H5N1 virus isolated in Southeast Asia
in 2004, was manufactured by sanofi pasteur, Swiftwater, PA, under contract to
NIAID. Because there are no manufacturers licensed in the United States to use
adjuvants in inactivated influenza vaccines, NIAID’s first step was to test an
H5N1 influenza vaccine made in a way that mimics the process used to make conventional
flu vaccines. The clinical data collected in this study are now available to
support the potential use of this vaccine should it be needed for an emerging
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 transplantation and immune-related illnesses, including autoimmune
disorders, 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 http://www.nih.gov.