Appendix B: Imvamune with Dr. Brett Petersen.
Imvamune is an attenuated, live,
replication-deficient vaccine containing Modified Vaccinia
Ankara, or MVA.
MVA is a vaccinia virus strain
that became replication-restricted
to avian cells following greater than 570 passages
in primary chicken embryo fibroblast cells
and is manufactured by Bavarian Nordic.
Unlike replication-competent smallpox vaccines,
Imvamune does not produce a lesion at the vaccination site
and does not present any risk for secondary transmission.
The vaccine is currently supplied as a sterile,
liquid-frozen preparation in single-dose 2 milliliter vials.
Imvamune contains no adjuvants and no preservatives,
but may contain trace amounts of residual host cell DNA
and protein, benzonase, and gentamicin.
The regulatory mechanism
by which Imvamune will be made available
and the populations covered, including individuals
with HIV infection or atopic dermatitis,
will be conveyed during a smallpox emergency event.
Since Imvamune vaccination consists of a two-dose series,
administered 4 weeks apart, the medical decision
for Imvamune vaccination
of these individuals should be assessed
against the risk-benefit of vaccinating the individual
with a single-dose of ACAM2000.
Individuals receiving primary vaccination
with Imvamune are not considered protected until 2 weeks
after the second dose.
The assessment should take
into account an individual's current immune status as well
as the individual's risk for smallpox infection.
Although persons vaccinated with Imvamune might have a lower risk
for serious adverse events, this might be outweighed
by the uncertainty in clinical effectiveness to prevent disease
and provide rapid protection.
Persons at high risk for complications
from replication-competent smallpox vaccines are often
at higher risk for severe smallpox.
For these reasons, persons with a known exposure
to smallpox virus should be vaccinated
with a replication-competent smallpox vaccine unless
severely immunodeficient.
Persons without a known smallpox virus exposure might still be
at high risk for developing smallpox infection depending
on the magnitude of the outbreak and the effectiveness
of the public health response.
Such persons will be defined by public health authorities
and should be screened for relative contraindications
to smallpox vaccination.
Persons with relative contraindications should be
vaccinated with Imvamune when available and authorized for use
by the Food and Drug Administration.
The route of administration of the vaccine is subcutaneous.
Imvamune 0.5 milliliter is injected under the skin,
preferably in the deltoid region of the non-dominant upper arm,
in two doses at 0 and 4 weeks for primary vaccinees.
Individuals previously vaccinated
against smallpox can receive a single 0.5 milliliter dose.
Imvamune does not produce a visible cutaneous reaction
following administration.
Imvamune is currently supplied
as a sterile frozen liquid product.
0.5 milliliters in 2 milliliter vials stored
at -25 degrees Celsius to -15 degrees Celsius.
Each vial contains one dose of Imvamune.
Each dose contains a minimum of 1 x 10 to the eighth
50% Tissue Culture Infective Dosage per milliliter
of live attenuated vaccinia virus, strain MVA-BN.
The efficacy of Imvamune against smallpox during an emergency is
unproven and cannot be clinically tested due
to the global eradication of the disease in humans.
However, the humoral immune response elicited
by Imvamune has been evaluated
in six published clinical studies.
Overall, Imvamune was determined
to elicit a humoral immune response
when evaluated using total IgG antibody enzyme-linked
immunosorbent assay, or ELISA,
and plaque reduction neutralization, or PRNT, assays.
The safety of Imvamune has been evaluated
in six published clinical trials involving a total
of 687 subjects: 562 vaccinia-naive
and 125 previously vaccinated.
Subjects ranged in age from 18 to 60 years and all were healthy
with the exception of 91 HIV-infected subjects.
The doses of vaccine administered in these trials
ranged from 1 x 10 to the sixth to 1 x 10 to the eight
50% Tissue Culture Infective Dosage.
Vaccine-naive subjects received two doses while
previously vaccinated subjects received only one dose.
Vaccine was administered either subcutaneously
or intramuscularly.
No deaths were reported.
Common vaccination complications reported were typical
for subcutaneously administered vaccines: local injection site
and general systemic reactions (fatigue,
headache, and myalgia).
Virtually all reactions were mild to moderate in severity
and all resolved without sequelae.
Imvamune does not produce a lesion at the vaccination site
and does not present any risk for secondary transmission.
During an emergency, Imvamune may be shipped frozen at less
than or equal to -15 degrees Celsius or refrigerated
at 2 to 8 degrees Celsius.
Upon receipt, store the vaccine in the following manner:
If the vaccine is received frozen, less than or equal
to -15 degrees Celsius, and requires storage before use,
maintain at frozen less than or equal to -15 degrees Celsius,
if freezer capacity is available, or refrigerated
at 2 to 8 degrees Celsius.
If the vaccine is received refrigerated at 2
to 8 degrees Celsius, and requires storage before use,
maintain Imvamune refrigerated at 2 to 8 degrees Celsius.
Once thawed, Imvamune may be used for up to 5 weeks
if maintained at 2 to 8 degrees Celsius.
Given the need for two doses, the length of time required
to acquire immunity, up to 6 weeks,
and lack of demonstrated efficacy of Imvamune,
all vaccinees should be instructed
to take protective measures in addition to being vaccinated
with Imvamune, such as avoiding crowded public places
until the outbreak in the community has been controlled
and avoiding direct contact with household members
who have been recently vaccinated
with a replication-competent smallpox vaccine
such as ACAM2000 or APSV
until their vaccination scab has fallen off their vaccination
site 2 to 4 weeks after vaccination.