This protocol is a joint project of the National Institutes of Health, the Centers for
Disease Control and the United States Army Medical Research Institute for Infectious
Diseases. It is designed to collect plasma from healthy employees of the Department of
Defense who have been vaccinated against anthrax. The collected plasma will be pooled to
make an anthrax-fighting antibody solution called anthrax immune globulin intravenous
(AIGIV). This solution will be used for:
- Animal experiments to test its effectiveness in preventing the development of anthrax
after inhalation exposure;
- Treating people severely ill with anthrax who are not improving with standard
antibiotic therapy; and
- Treating people exposed to spores of the bacteria that cause anthrax to try to prevent
development of the disease.
Healthy volunteers between 18 and 65 years of age who have received at least four doses of
the anthrax vaccine and who meet the criteria for blood donors may be eligible to
participate in this study. Volunteers will be recruited from Department of Defense civilian
and military employees. Candidates will be screened with an interview and blood tests.
Participants will undergo the following procedures:
- Have a health history screen for donating plasma
- Measurement of heart rate, blood pressure and temperature
- Fingerstick to check hemoglobin level
- Blood tests for HIV, hepatitis B and C, syphilis and other infectious diseases
- Blood test for anthrax antibody levels
- Plasmapheresis to collect blood plasma (the liquid part of the blood)
In plasmapheresis, whole blood is drawn through a needle placed in an arm vein. The blood
flows into a cell separator machine, where it is spun to separate the plasma from the blood
cells. The plasma is collected in a plastic bag in the machine, while the rest of the blood
is returned to the donor through the needle in the arm. During the procedure, the donor is
given a blood thinner called citrate to prevent the blood from clotting while it is in the
cell separator machine. The procedure lasts from 60 to 90 minutes. Only a small fraction
of the body's total plasma is removed, and it is quickly replaced by the body with no
long-term health effects. Participants may be requested to donate plasma as often as every 3
to 4 days or as infrequently as once a month for a maximum of six donations.
Inhalational anthrax infection is associated with a 60-100% mortality rate, depending on the
rapidity with which appropriate antimicrobial therapy is initiated. Experiments using an
animal model of inhalational anthrax suggest that adjunctive therapy with equine-derived
anti-anthrax antisera may be associated with higher survival rates, however no human-derived
antisera are currently available. The purpose of this protocol is to provide a mechanism
for obtaining high-titer anti-anthrax immunoglobulin by plasmapheresis of human volunteers
who have recently received a course of anthrax vaccination. Volunteers are Department of
Defense (DoD) employees and military personnel who are within 3 to 12 weeks of having
received a fourth or greater dose of AVA if four to six total inoculations were given, or
within 6 months of the last dose if seven or more AVA inoculations were given. All
vaccinees were vaccinated as a requirement of their tour of duty and will otherwise meet all
blood donor eligibility criteria, in accord with Food and Drug Administration (FDA)
requirements and American Association of Blood Banks (AABB) standards. Plasmapheresis will
be accomplished using licensed apheresis devices and standard collection techniques, and
products will meet all blood safety testing requirements currently mandated by the FDA.
Plasma components collected under this protocol will be stored in the frozen state as fresh
frozen plasma (FFP) until a protocol for administration of these components to human
patients critically ill with inhalational anthrax infection has been reviewed and approved
by the IRB's of NIH, CDC, and USAMRIID. Following this approval, products will undergo
standard Cohn-Oncley fractionation into a concentrated immunoglobulin preparation suitable
for intravenous use, to be designated anthrax immune globulin intravenous (AIGIV).
Intravenous administration of products derived from plasma collected under this protocol,
whether as single-donor FFP or as AIGIV, will occur under a Phase I/II trial involving an
Investigational New Drug (IND) exemption, with the IND held by the Centers for Disease
Control and Prevention (CDC). The plasma products collected under this protocol will also
be used in pharmacokinetic, dose finding, and efficacy studies in animals, and to establish
a repository of reference serum standards at the CDC. This study represents a collaborative
effort between the DTM/NIH, CDC, and DoD.
Age range 18 to 65 years.
Weight greater than 110 pounds.
Fingerstick hemoglobin greater than or equal to 12.5 g/dL.
No known heart, lung, kidney disease, or bleeding disorders.
No history of hepatitis since age 11.
No history of intravenous injection drug use.
No tattoos or non-sterile skin piercing within the past 12 months.
No history of engaging in high-risk activities for exposure to AIDS or hepatitis viruses,
as defined in the DTM "Donor Alert."
Female subjects should not be pregnant.
Completion of a primary AVA vaccination series (0, 2, 4 weeks and 6 months) and be within
3 to 12 weeks of receiving a dose at 6 months, 12 months, or 18 months; or within 6 months
of an annual booster.