Current Trends
Rabies Vaccine, Adsorbed: A New Rabies Vaccine for Use in Humans
Rabies Vaccine, Adsorbed (RVA, Michigan Department of Public
Health), a new cell culture-derived rabies vaccine for use in
humans,
was licensed on March 18, 1988, for both preexposure and
postexposure
prophylaxis. The Biologics Products Program, Michigan Department
of
Public Health, developed, produces, and distributes the vaccine.
RVA
is currently available only to residents of the state of Michigan,
but
plans are being developed for out-of-state distribution.
The vaccine is prepared from the Kissling strain of rabies
virus
adapted to a diploid cell line of the fetal rhesus lung (1). The
virus
is inactivated with *gb-propiolactone and concentrated by
adsorption
to aluminum phosphate (AlPO4). AlPO4 may also serve as an
adjuvant.
RVA differs from the rabies vaccine currently available in the
United States, the human diploid cell rabies vaccine (HDCV)
produced
by Merieux Institute, Inc. A different virus strain, cell line,
and
concentration process are used in making RVA, and, because RVA is
adsorbed to AlPO4, it is liquid rather than lyophilized.
After preexposure (2), simulated postexposure (3), and booster
vaccination (4), acceptable levels of rabies-neutralizing antibody
have been found in over 99% of 3,000 persons tested. The
recommended
timing of vaccinations with RVA is identical to that of
vaccinations
with HDCV. Preexposure vaccination consists of three 1-mL doses,
one
dose to be administered intramuscularly (IM) in the deltoid area
on
days 0, 7, and 28. Preexposure booster doses of RVA (one 1-mL IM
dose)
should be administered according to previous guidelines (5). In
contrast to HDCV (6), the antibody response and side effects after
intradermal administration of RVA have not been studied. RVA
should
not be used intradermally.
Postexposure vaccination of individuals who have not
previously
been immunized consists of five 1.0-mL doses of RVA, one dose to
be
administered IM in the deltoid (IM in the anterior lateral thigh
for
infants) on days 0, 3, 7, 14, and 28. At the same time that the
first
1-mL dose of RVA is administered on day 0, rabies immune globulin
(RIG) 20 IU/kg is administered as a separate injection. Up to half
of
the RIG is infiltrated around the site of the bite, if feasible;
the
rest is administered IM in the gluteal area (for infants, IM in
the
anterior lateral thigh). Rabies vaccine and RIG should never be
administered into the same limb. If exposed to rabies, persons who
were previously vaccinated with HDCV or RVA (preexposure or
postexposure) and persons who were immunized with other rabies
vaccines and who had a documented neutralizing antibody response
after
vaccination should receive only two 1-mL IM booster doses of RVA,
one
on day 0 and one on day 3. Testing to document primary
seroconversion
is recommended only for persons whose immune system is suppressed
by a
disease or medication.
Reactions after primary vaccination with RVA appear similar in
nature and frequency to those observed with HDCV. They include
local
reactions (pain and redness or swelling at the injection site) in
85%-90% of volunteers receiving RVA and mild systemic reactions
(fever, nausea, and arthralgia) in 10%. Physicians and other
health-care providers are urged to report any other type of
reactions
to either RVA or HDCV to the manufacturer or the Food and Drug
Administration on CDC form 55.19 9/82 (formerly CDC form 4.650),
which
is available from state and local health departments.
The use of preexposure booster doses of HDCV has been limited
because approximately 6% of individuals who receive both primary
and
booster vaccinations with HDCV develop a serum sickness like an
allergic reaction (7,8). These reactions are thought to be due to
the
presence of a small amount of human serum albumin that has been
rendered allergenic by the *gb-propiolactone used in making HDCV
(9,10). Human serum albumin is not a component of the medium used
to
grow the rabies virus for RVA and, therefore, is not present when
*gb-propiolactone is added to inactivate the virus. However,
systemic
allergic reactions have also occurred in four persons after they
received booster doses of RVA, for a rate of less than 1%.
Reported by: Biologics Products Program, Michigan Dept of Public
Health. Quinnan GV, MD, Fitzgerald EA, PhD, Center for Biologics
Evaluation and Research, Food and Drug Administration. Viral and
Rickettsial Zoonoses Br, Div of Viral Diseases, Center for
Infectious
Diseases, CDC.
References
Burgoyne GH, Kajiya KD, Brown DW, Mitchell JR. Rhesus diploid
rabies vaccine (adsorbed): a new rabies vaccine using FRhL-2
cells. J Infect Dis 1985;152:204-10.
Berlin BS, Mitchell JR, Burgoyne GH, et al. Rhesus diploid
rabies
vaccine (adsorbed), a new rabies vaccine: results of initial
clinical studies of preexposure vaccination. JAMA 1982;
247:1726-8.
Berlin BS, Mitchell JR, Burgoyne GH, Brown WE, Goswick C.
Rhesus
diploid rabies vaccine (adsorbed), a new rabies vaccine: II.
Results of clinical studies simulating prophylactic therapy
for
rabies exposure. JAMA 1983;249:2663-5.
Berlin BS, Goswick C. Rapidity of booster response to rabies
vaccine produced in cell culture (Letter). J Infect Dis
1984;150:785.
Immunization Practices Advisory Committee. Rabies prevention:
supplementary statement on the preexposure use of human
diploid
cell rabies vaccine by the intradermal route. MMWR
1986;35:767-8.
Centers for Disease Control. Systemic allergic reactions
following
immunization with human diploid cell rabies vaccine. MMWR
1984;33:185-7.
Dreesen DW, Bernard KW, Parker RA, Deutsch AJ, Brown J. Immune
complex-like disease in 23 persons following a booster dose of
rabies human diploid cell vaccine. Vaccine 1986;4:45-9.
Swanson MC, Rosanoff E, Gurwith M, Deitch M, Schnurrenberger
P,
Reed CE. IgE and IgG antibodies to *gb-propiolactone and human
serum albumin associated with urticarial reactions to rabies
vaccine. J Infect Dis 1987;155:909-13.
Anderson MC, Baer H, Frazier DJ, Quinnan GV. The role of
specific
IgE and beta- propiolactone in reactions resulting from
booster
doses of human diploid cell rabies vaccine. J Allergy Clin
Immunol
1987;80:861-8.
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