Updates on Pandemic Flu Vaccine Trials to be Presented
at 44th Annual IDSA Meeting
Preliminary results from clinical trials testing two different
pandemic flu vaccine approaches — one a prime-boost strategy
using different subtypes of H5N1 vaccines, the other an H5N1 vaccine
delivered into the skin (intradermal) rather than the muscle — will
be presented at the 44th Annual Meeting of the Infectious Diseases
Society of America being held in Toronto Oct. 12-15. The presentations
are scheduled for a late-breaker session on Friday afternoon, Oct.
Funding for the trials comes from the National Institute of Allergy
and Infectious Diseases (NIAID), one of the National Institutes
of Health. Reporters may call the NIAID News Office at 301-402-1663
to speak with NIAID Director Anthony S. Fauci, M.D., who is available
to comment and provide perspective on these preliminary findings.
Preliminary Results Suggest Priming Boosts Immune Responses
to Variant H5N1 Vaccine
Presentation time: Late-Breaker Session, Friday, Oct. 13,
2006, 5:00 p.m.
Presenter: Nega Ali Goji, M.D., University of Rochester Medical
Center, Rochester, NY
If a pandemic influenza strain was identified, it would likely
take several months to make a vaccine against it, and stimulating
protective immunity with the vaccine would likely require more
than one dose. Giving people two doses of H5N1 influenza vaccine
as a pandemic is evolving would be logistically difficult, however,
so researchers have been urgently investigating alternative strategies.
One such alternative is to prime people ahead of time with a related
vaccine so that only a single dose of vaccine is required when
the pandemic emerges. A team of researchers led by University of
Rochester Medical Center investigators Nega Ali Goji, M.D., and
John J. Treanor, M.D., recently tested this hypothesis. They compared
the immune response to a single 90-microgram dose of one variant
of avian flu vaccine in two groups of adults: those who had received
a different variant of H5N1 avian flu virus vaccine some eight
years earlier and those without pre-exposure to any H5N1 virus
In late 1997-98, soon after the first case of direct bird-to-human
transmission of an H5N1 flu virus occurred in Hong Kong, NIAID
funded the production of an experimental vaccine made from the
Hong Kong virus and tested it in a small clinical trial conducted
at the University of Rochester in healthy adults (see reference).
Thirty-seven individuals who received two doses of the Hong Kong
H5N1 vaccine in that trial served as the “primed” population in
the current study.
The booster dose in the current study — an experimental
inactivated H5N1 virus vaccine produced for NIAID by sanofi pasteur,
the vaccines business of the sanofi-aventis Group of Paris — is
based on an H5N1 flu virus from Vietnam. The Hong Kong virus is
related to the Vietnam virus but belongs to clade 3, which refers
to its branch on an evolutionary tree of the H5N1 viruses in Asia,
while the Vietnam virus belongs to clade 1.
In their trial, the Rochester team found that more than twice
as many of the individuals who had received the priming dose of
clade 3 H5N1 vaccine responded with substantial antibody levels
to a single dose of clade 1 H5N1 vaccine than did those with no
prior H5N1 exposure. Dr. Treanor says that these early but promising
data indicate that priming with an antigenic variant vaccine before
a pandemic occurs may be one strategy used to help control a pandemic.
“These preliminary findings need to be confirmed in larger studies,
but they offer the intriguing possibility that pre-pandemic priming
with existing H5N1 vaccines may boost the immune response to a
different H5N1 vaccine tailor-made years later to thwart an emerging
human influenza pandemic,” says Dr. Fauci.
Third Dose of Intramdermal H5N1 Vaccine Well-Tolerated
but does Not Improve the Immune Response
Presentation Time: Late-Breaker Session, Friday, Oct. 13,
2006, 5:15 p.m.
Presenter: Shital M. Patel, M.D., Baylor College of Medicine, Houston,
Previous studies have suggested that lower dosages of seasonal
flu vaccine given intradermally may work as well as higher dosages
of the same vaccine given intramuscularly, enabling public health
officials to “stretch” available doses of vaccine in a time of
shortage. To test this principle with an H5N1 pandemic flu vaccine,
NIAID initiated a vaccine trial to compare immune responses generated
by an H5N1 vaccine given by the intradermal or the intramuscular
route. The H5N1 vaccine formulations were produced for NIAID by
Wendy Keitel, M.D., Shital M. Patel, M.D., and their Baylor College
of Medicine colleagues conducted the trial. Results of their initial
two-dose study among 100 participants indicated that antibody responses
among volunteers given 3 or 9 micrograms of vaccine intradermally
were similar to the antibody responses seen among volunteers given
15 micrograms intramuscularly: 4 percent, 5 percent, and 12 percent
of volunteers, respectively, had a significant increase in antibody
levels after two doses. Those given 45 micrograms by the intramuscular
route, however, showed a significantly higher response rate: 56
percent of volunteers in this group responded.
In the current study, the Baylor team enrolled 77 healthy adults
between the ages of 18 and 40 who had previously received two doses
of the same vaccine one month apart and gave them a third dose
of vaccine 6 months later to see if it boosted their antibody response.
The participants, again divided into four groups, received either
3 or 9 micrograms intradermally or 15 or 45 micrograms intramuscularly.
The dosages of vaccine were limited by the formulations available.
According to Dr. Patel, a quarter or less of the participants
in the study groups given the vaccine intradermally or intramuscularly
at 15 micrograms had a significant antibody response after the
third dose, while nearly two-thirds of the volunteers in the group
that received 45 micrograms intramuscularly had a similar response.
For each dosage by either route of administration, the results
show that giving a third dose of the vaccine 6 months later increased
antibody titers to levels similar to those achieved after the first
“This small pilot study demonstrates that multiple doses of an
inactivated H5N1 vaccine given by either the intradermal or the
intramuscular route are safe and well tolerated,” says Dr. Fauci. “It
also provides a strong rationale for testing higher dosages of
H5N1 vaccine given intradermally.” Plans are under way to directly
compare the immune responses generated by vaccinating either into
the skin or into the muscle with an H5N1 vaccine containing higher
levels of the same amount of antigen.
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.
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
its programs, visit www.nih.gov.