The Vaccine Research Center has begun a five-year study of Anthrax
Vaccine Adsorbed (AVA), the only human vaccine approved for the
bacterium, Bacillus anthracis.
Sponsored by a $4.2 million grant from the Centers for Disease
Control and Prevention (CDC) and under the direction of Robert Mittler,
assistant professor of surgery and a VRC researcher, the program
will assess and compare the efficacy of three different vaccine
regimens in rhesus macaque monkeys starting in June. Research-ers
also hope to determine the strength of protective immunity against
anthrax after inoculation.
No live anthrax bacteria will be used in theYerkes study; Mittler
and his team instead will use harmless proteins derived from anthrax
toxins to assess the immune response promoted by AVA.
The study will involve 33 rhesus macaques equally divided among
three groups. One group will receive a course of three AVA shots
at full concentration. A second group will be vaccinated with three
shots diluted to 10 percent strength, and the third group of monkeys
will be inoculated with three shots at 5 percent of the full concentration.
A single monkey in each group will serve as a control and will receive
a placebo shot.
When inhaled, anthrax spores enter specialized immune cells called
macrophages, where they germinate into vegetative cells that produce
two deadly toxins that kill cells. Death can result as quickly as
two days after these toxins enter the circulatory system. AVA produces
antibodies against a component of the toxin called protective antigen
(PA). By blocking the activity of PA, these antibodies prevent the
toxins from entering and subsequently killing cells.
Since 1970, when the U.S. Food and Drug Administration licensed
AVA for human use, more than 2 million doses of the vaccine have
been administered, mostly to members of the military. Like most
vaccines, AVA has side effects, including redness and swelling at
the injection site.
Concerns that it also may have more serious systemic effects, however,
were raised in the mid-1990s after a number of Gulf War veterans
who received AVA began experiencing an unusual variety of neurological
disorders that came to be called Gulf War Syndrome. Pressure to
study this unusual malady prompted Congress to mandate new research
on AVA. The CDCs AVA research program emerged from this initiative.
Although a number of new anthrax vaccines are under development,
BioPort Corp. of Lansing, Mich., is the nations sole producer
of anthrax vaccine.
Mittler described the manufacturing process for AVA as crude,
based on modern standards of vaccine production. Bacillus anthracis
are grown in large fermentation vats, then filtered out, leaving
behind an anthrax-free broth of proteins produced by the bacteria.
These proteins are subsequently used to immunize human recipients.
The threat of anthrax as a bioterrorism agent became a public reality
last fall following a series of mailings of anthrax spores and the
deaths of five people. In the wake of these attacks, federal funding
for research on anthrax, smallpox, and other potential bioterrorism
agents has increased substantially.
AVA has drawn criticism for the large number of shots associated
with the vaccine regimen and the amount of time needed to raise
protective immunity. No other human vaccine requires as many shots
as AVA, noted Mittler.
sWith the resurgence of government interest and funding for anthrax
research, BioPort may soon face some competition. The technology
exists today, Mittler said, to clone those specific
proteins that produce the anthrax toxins and thus develop a much
more refined and targeted anthrax vaccine.
Mittlers co-investigators at VRC are researcher Chris Ibegbu,
VRC Director Rafi Ahmed and veterinarian Denyse Levesque.