RABIES VACCINE ( Human Diploid Cell Rabies Vaccine (HDCV))
Modern Vaccines:
Human Diploid Cell Rabies Vaccine (HDCV)
The introduction of Modern Tissue Culture Vaccines (HDCV)
is a great advance in Rabies management. The vaccine is more
potent and safer than conventional NTV and immunization
requires fewer injections of smaller volume with relatively few
side-effects. In 1960s, workers at Wistar Institute in Philadelphia
selected the Human Diploid Cell Strain Wl-38 for virus
propagation to avoid the difficulties inherent in the use of
Primary Tissue Cultures such as induction of allergy to animal
proteins". The vaccine thus developed, the Human Diploid Cell
vaccine (HDCV), containing concentrated and purified virus
evoked much better immune responses'. The technical
advances leading to the development of the vaccine included
adaptation of the Pitman Moore strain of virus to Wl-38 cells',
inactivation of cell free virus by p-propiolactone, and
concentration ofthevirusbyulta-filtration'// Currently. HDCV is
produced in MRC-5 human fibroblasts that are inoculated with
the Pitman Moore strain. Potency is assessed by National
Institutes of Health tests in Mouse brain and is at least 2.5 IU per
dose.
Although, an exact conversion for
determining antibody titre equivalency
does not exist, an antibody titre of 1 :50
determined by RFFIT (Rapid Fluorescence focus Inhibition Test) is approximately equivalent to 1 IU/ml. The
WHO specifies a titre of 0.5 IU/ml as an acceptable response
(equivalent to 1:25 by RFFIT). Following I/M administration of
HDC Rabies Vaccine, rabies antibodies appear in the serum
within 7-10 days, peak within 30-60 days and persist for at
least 1 year'".
The Human Diploid Cell Rabies Vaccine was first licensed in
Europe for Pre-exposure and Post-exposure immunization of
The Human Diploid Cell Rabies vaccine
is regarded as the "Gold Standard"
in Rabies Vaccines and has been given
to more than 1.5 million people, worldwide.
humans in 1976. HDCV was licensed in the United States in
June, 1980.
The Human Diploid Cell Rabies vaccine is regarded as the
"Gold Standard" in Rabies Vaccines and has been given to more
than 1.5 million people, worldwide. Its protective efficacy in
situations of heavy exposure has been shown in the Islamic
Republic of Iran where none of the 45 persons who received
Post-exposure treatment with this vaccine developed rabies
following severe bites by Rabid dogs or wolves. Studies with
Human Diploid Cell Vaccine have shown that 10 years after the
Pre-exposure series followed by a single booster dose after 1
year, more than 96% of the vaccines still have neutralizing
antibodies against rabies viTUS39
Several studies have been conducted to assess antibody
responses to Modern Tissue Culture Rabies Vaccines and the
important findings are as follows:-
a. Important immune responses to Rabies vaccines include
antibodies to G-protein of the viral envelope.
b. Antibodies appear 7-10 days after the first dose.
C. It is not mandatory to check RnAb litres after Pre-
exposure or Post-exposure immunization with newer
TCVs unless the
individual is
immuno-supressed,
on anti-malarial
therapy or has
received anaesthesia.
d. HIV infected patients could be poor responders to Rabies
vaccines and should be monitored by RnAb assessment".
e. Individuals more than 50 years of age show a reduced
response than younger subjects but all sero-convert after
5 doses.
f. Vaccinees of HLA group B7 and Dr2 show early and high
antibody responses whereas those of HLA
group Dr3 respond late with lower antibody
titres.
Only due to the high cost of previously
available HDC vaccine, other tissue culture
vaccines like PVRV and PCEC were
developed.
OBSERVATION OF ANIMAL :
Observation of animal for possible rabies is applicable only
to dogs & cats and not to other animals. Rabies is widely
prevalent in animals in India (enzootic) and stray animal menace
is rampant. Since NTV (Semple vaccine) is reactogenic and the
sera being scarce, the judicious and rational use of post
exposure immunization becomes important to the physician.
Consequently, unnecessary use of vaccines & sera is to be
avoided or minimized bearing in mind the risk of rabies, cost of
modern vaccines & sera and reactogenicity of the Semple
vaccine. This will be possible if the biting animal is observed.
The biting animal viz., dog and cat wherever possible
should be observed for at least 10
days. The rationale is if the animal
is infected, its saliva is infective up
to 5 days before signs of rabies
appear in it, and once the signs of
rabies develops it will invariably die in about another 5 days
maximum. In India, (even vaccinated) dogs/cats including pets,
are presumed to be rabid/infective at the time of biting. Hence,
it should not be killed or chased away but be observed for the
following signs for IO days:-
1. Any change in its normal behaviour-either undue
aggression or depression.
2. Running aimlessly and attacking others without
any provocation.
3. Becomes too drowsy and withdraws itself to a
corner.
4. Excessive salivation.
5. Change in its voice/bark.
6. Refusal to feed or eating unusual objects like stone, paper,
wood, metal objects, etc.
7. Death of the animal.
The occurrence of any one of the above signs, strongly
indicates rabies. Consequently, the suspect dog/cat should be
examined by a qualified veterinarian and if facilities are
available, the animal is humanely killed and its brain examined
by laboratory methods for confirmation of rabies. If veterinary
facilities are not available, the animal is SUSPECTED TO BE RABID
and correct, complete post-exposure immunization is important
and life saving.
It involves administration of
(a) Anti-Rabies vaccine-category II & category III exposure
(b) Anti-rabies Serum in severe or category III exposure
Because of long and variable incubation period of rabies,
immunization must be started at the earliest, to ensure tha
the individual is immune before the rabies virus reaches th(
nervous system.
Indications for Anti-Rabies Immunization
It should be started immediately when a person is
bitten, scratched or licked under the following
conditions:
1. The animal is stray and not available for
observation (presumed rabid)
2. The animal shows clinical signs of rabies
(suspect rabies).
3. The animal is proved positive for rabies by
laboratory examination (confirmed rabies).
Situations where anti-rabies immunizations is not
indicated/required
1. Drinking of boiled, even heated milk, of rabid
animal.
2. Biting dog or cat has remained healthy & alive for
10 days after the bite.
3. Mere touching of a rabid animal (no contact with
saliva/urine).
4. A bite or scratch over clothing without tearing or piercing it
and no sign of injury of the skin.
5. Unprovoked & accidental bites by rodents, rats, mice, hares,
rabbits, birds, bats and insects.
In an endemic and enzootic country like India, where every
animal bite is considered a "risk" immediate starting of vaccine
in "low risk" exposures (class II of WHO classification) and serum
and vaccine in "high risk" (class III of WHO classification)
exposures is strongly recommended. Simultaneously, the
dog/cat is observed for 5 days. If the animal remains healthy up
to 5 days, it may be assumed that it is not rabid, and the
treatment discontinued, and the dog/cat further observed for
10 days. During this period, if the dog/cat becomes sick and
rabies is suspected/confirmed/ dies (cause not known, then
suspected rabies) or absconds and becomes unavailable for
observation, the treatment should be continued (not restarted
afresh) and completed as per the original schedule.
Rabivax is a unique rabies
vaccine in the world. It is the
only HOC rabies vaccine available
in the liquid-adsorbed form which is
Highly Stable even when stored
at ~7°C
In case of Rabies vaccines, the HDC vaccine has been
recognized as the 'Gold Standard' the world over. Even the WHO
in its position paper of 2002 (on Rabies) mentions HDC rabies
vaccine as the Gold Standard. The HDC vaccine was available in
India but phased out due to it's high cost.
After years of Research & Development, Serum Institute of
India Ltd, Pune is proud to introduce the indigenously
manufactured HDC rabies vaccine (liquid, adsorbed) on the
Pitman Moore strain, used world-wide i.e.
RABIVAX
Rabivax is a unique rabies vaccine in the world. It is the only HDC
rabies vaccine available in the adsorbed form. which makes it a
Ready-to-use vaccine, as there is no dissolution step. The details
of its features:
Features
• Cultured on Human Diploid Cells
• Contains the acclaimed Pitman Moore strain
• Unique Ready-to-use Liquid vaccine
(adsorbed)
• Highly Stable: Potency maintained
even when stored at
37 °C for 4 weeks
• Free of antibiotics
Clinical Features
The several clinical studies that have
been conducted have shown that
clinicians can expect the following from
RABIVAX:
High Efficacy
• Excellent immunogenicity and efficacy
• 100% seroconversion by day 14
• High antibody titers, well over the minimum protective
level
• Level of antibodies unaffected by use of RIG
High Safety
Safe in individuals allergic to other cell culture vaccine
components
• egg proteins * avian proteins
• neomycin, chlortetracycline, streptomycin, polymyxin B
Safe in individuals allergic
to other cell culture vaccine
components
' egg proteins ' avian proteins
• neomycin, chlortetracycline,
streptomycin, polymyxin B
*****************************************************
RABIES VACCINE RESUS LUNG CELL DIPLOID VACCINE
DESCRIPTION:
Rabies Vaccine Adsorbed is a sterile, cell- culture derived rabies vaccine for
pre- and post- exposure prophylaxis in humans. It is prepared with the CVS
Kissling/MDPH strain of rabies virus. The virus is propagated in a diploid cell
line derived from fetal rhesus lung cells (FRhL-2 cell line) in a serum-free,
chemically defined, antibiotic-free medium. The virus harvest, which is
clarified by centrifugation and filtration, is inactivated with
betapropiolactone. After inactivation, the virus is adsorbed to aluminum
phosphate.
The final vaccine is a suspension containing 2.5 international units or more of
rabies antigen per 1.0 mL dose. It contains no more than 2.0 mg aluminum
phosphate per mL and also contains 0.01% sodium ethylmercurithiosalicylate
(thimerosal) as a preservative. The solution is a light pink color due to the
presence of phenol red.
Rabies Vaccine Adsorbed is intended for intramuscular (IM) injection. CAUTION:
THIS VACCINE IS NOT FOR USE BY THE INTRADERMAL (ID) ROUTE.
ACTIONS/CLINICAL PHARMACOLOGY:
The immune response to rabies vaccines can be ascertained by measuring antibody
directed against rabies virus by means of the rapid fluorescent focus inhibition
test (RFFIT). Serum antibody levels against rabies virus are usually expressed
in terms of international units or serum titers. The definition of a minimally
acceptable antibody titer in vaccinees varies among laboratories and is
dependent on the type of test performed. The Centers for Disease Control
considers complete virus neutralization at a 1:5 serum dilution by the RFFIT a
minimally acceptable response to pre-exposure vaccination. The World Health
Organization specifies that a minimum titer of 0.5 international units is an
adequate response to vaccination.
In field trials of Rabies Vaccine Adsorbed, 99% or greater of 1,567 persons who
had not been immunized previously against rabies responded with serum titers of
0.5 international units (a dilution titer of approximately 1:25) or greater by 2
weeks after the last of 3 IM injections of Rabies Vaccine Adsorbed given over a
3- or 4-week period. At 9 to 12 months post-immunization, 97% of 605 persons had
antibody titers at or above a level of 0.1 international units (a 1:5 dilution
of serum). In addition, 97% or more of 2,148 persons previously immunized with
Duck Embryo Rabies Vaccine, Human Diploid Rabies Vaccine or Rabies Vaccine
Adsorbed showed 4-fold increased antibody titers following a single booster
injection of Rabies Vaccine Adsorbed.
In post-exposure field trials and clinical simulations of post-exposure
prophylaxis, 5 doses of Rabies Vaccine Adsorbed, in conjunction with Rabies
Immune Globulin, induced active antibody production in all previously
unvaccinated persons between the seventh and fourteenth day following initiation
of treatment. In post-exposure rabies prophylaxis, Rabies Immune Globulin is
given concomitantly with the first injection of rabies vaccine to provide
immediate passive immunoprophylaxis. If not given when vaccination was begun,
Rabies Immune Globulin may be given up to 7 days after administration of the
first dose of vaccine.
Rabies Vaccine Adsorbed has been used successfully to immunize both adults and
children 6 years of age and older.
There have been reports of possible vaccine failures when human diploid cell
rabies vaccine (HDCV) has been administered in the gluteal area. Subcutaneous
fat in the gluteal area may interfere with the immunogenicity of HDCV. (REF. 1-
3) It is not known if an adequate response would be obtained after gluteal
administration of Rabies Vaccine Adsorbed. Therefore, adults and older children
should receive this vaccine in the deltoid muscle. For younger children the
anterolateral aspect of the thigh is also acceptable.
INDICATIONS AND USAGE:
Rabies Vaccine Adsorbed is indicated for immunization against rabies in the
following circumstances: PRIMARY PRE-EXPOSURE IMMUNIZATION which is intended to
induce immunity before exposure to the virus; PRE-EXPOSURE BOOSTER IMMUNIZATION
which is intended to augment or reinforce the level of immunity induced by
previous immunization against rabies; or POST- EXPOSURE PROPHYLAXIS which is
given to persons who, in the judgment of the treating physician, may have been
exposed to rabies virus. Each circumstance requires a different schedule of
injections.
A. PRIMARY PRE-EXPOSURE VACCINATION (see Table 1): Pre-exposure vaccination is
given to persons who are at greater than usual risk of possible rabies exposure
by reason of occupation or avocation. The list of such persons includes, but is
not limited to, veterinarians and staff, certain laboratory workers, animal
handlers and persons spending time (e.g., 1 month or more) in foreign countries
where canine rabies is enzootic. Persons whose vocational or avocational
pursuits bring them into contact with potentially rabid dogs, cats, foxes,
skunks, raccoons, bats or other species at risk of having rabies should also be
considered for pre-exposure prophylaxis.
Pre-exposure vaccination is given as a series of 3 individual injections of
Rabies Vaccine Adsorbed with the second and third injections being given 7 and
21 or 28 days after the first injection, respectively. Pre-exposure vaccination
does NOT eliminate the need for prompt post- exposure prophylaxis following an
exposure; it only eliminates the need for Rabies Immune Globulin and reduces the
number of injections of rabies vaccine needed for post-exposure prophylaxis.
Criteria for pre-exposure vaccination are summarized in Table 1.
B. PRE-EXPOSURE BOOSTER VACCINATION (see Table 1): Pre-exposure booster
vaccination is given to persons who have received previous rabies vaccination
and remain at increased risk of rabies exposure by reasons of occupation or
avocation. Persons who work with live rabies virus in research laboratories or
vaccine production facilities (continuous-risk category; see Table 1) should
have a serum sample tested for rabies antibody every 6 months. Booster doses of
vaccine should be given to maintain a serum titer corresponding to at least
complete neutralization at a 1:5 serum dilution by the RFFIT. The frequent-risk
category includes other laboratory workers, such as those doing rabies
diagnostic testing, spelunkers, veterinarians and staff, animal-control and
wildlife officers in areas where animal rabies is epizootic, and international
travelers living or visiting (for >30 days) in areas where canine rabies is
endemic. Persons among this group should have a serum sample tested for rabies
antibody every 2 years and, if the titer is less than complete neutralization at
a 1:5 serum dilution by the RFFIT, should have a booster dose of vaccine.
Alternatively, a booster can be administered in lieu of a titer determination.
Veterinarians and animal-control and wildlife officers working in areas of low
rabies enzooticity (infrequent- exposure group) do not require routine pre-
exposure booster doses of Rabies Vaccine Adsorbed after completion of primary
pre-exposure vaccination (Table 1).
A single booster injection of Rabies Vaccine Adsorbed has been shown to increase
antibody titers in persons who have previously been immunized with Rabies
Vaccine Adsorbed or Human Diploid Cell Rabies Vaccine. Persons who have been
shown to have developed antibody responses to a previous series of injections of
Duck Embryo Rabies Vaccine also respond to a single booster dose of Rabies
Vaccine Adsorbed.
TABLE 1. PRE-EXPOSURE VACCINATION CRITERIA*/*
PRE-EXPOSURE VACCINATION. Primary pre-exposure vaccination consists of 3 doses
of Rabies Vaccine Adsorbed, 1.0 mL, IM (i.e., deltoid area), 1 each on days
0, 7 and 21 or 28. Administration of routine booster doses of vaccine depends
on exposure risk category as noted below.
Criteria for Pre-Exposure Vaccination
Risk Category Nature of Risk Typical Populations Pre-Exposure Regimen
----------------------------------------------------------------------------------------------------------------------------------------------------------------------
Continuous Virus present Rabies research Primary course.
continuously, laboratory Serology every
often in high workers*; 6 months; booster
concentrations. rabies biologics vaccination when
Aerosol, mucous production antibody level
membrane, bite workers. falls below
or non-bite acceptable level.**
exposure possible.
Exposure may go
unrecognized.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Frequent Exposure usually Rabies diagnostic Primary course.
episodic, with laboratory Serologic testing or
source recognized, workers,* booster vaccination
but exposure spelunkers, every 2 years.**
may also be veterinarians and
unrecognized. staff, and
Aerosol, mucous animal-control and
membrane, bite wildlife workers in
or non-bite rabies enzootic
exposure. areas; travelers
visiting foreign
areas of enzootic
rabies for more
than 30 days.
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Infrequent Exposure nearly Veterinarians and Primary course.
(greater than always episodic animal-control No serologic
population with source and wildlife testing or booster
at large) recognized. workers in areas vaccination.
Mucous membrane, of low rabies
bite or non-bite enzooticity.
exposure. Veterinary
students.
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Rare Exposure always U.S. population at No vaccination
(population episodic. large, including necessary.
at large) Mucous membrane individuals in
or bite with rabies enzootic
source areas.
recognized.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
*/*References 4 and 5.
*Judgment of relative risk and extra monitoring of immunization status is the
responsibility of the laboratory supervisor (see U.S. Department of Health
and Human Services' Biosafety in Microbiological And Biomedical Laboratories,
1984).
**Pre-exposure booster vaccination consists of 1 dose of Rabies Vaccine
Adsorbed, 1.0 mL dose intramuscular (deltoid muscle). Minimum acceptable
antibody level is complete virus neutralization at a 1:5 serum dilution by
RFFIT. Administer booster dose if titer falls below 1:5.
TABLE 2. RABIES POST-EXPOSURE PROPHYLAXIS GUIDE*/*
Post-Exposure
Evaluation and Prophylaxis
Animal Type Disposition of Animal Recommendations
-------------------------------------------------------------------------------------------------------------------------------------------------------------------
Dogs and cats Healthy and available Should not begin
for 10 days' prophylaxis unless
observation animal develops
symptoms of rabies.*
Rabid or suspected rabid Immediate vaccination.
Unknown (escaped) Consult public health
officials.
-----------------------------------------------------------------------------------------------------------------------------------------------------------------
Skunks, raccoons, Regarded as rabid Immediate vaccination.
bats, foxes and most unless geographic
other carnivores; area is known to be
woodchucks free of rabies
or until animal
proven negative by
laboratory tests**
----------------------------------------------------------------------------------------------------------------------------------------------------------------
Livestock, rodents Consider individually Consult public health
and lagomorphs officials. Bites of
(rabbits and hares) squirrels, hamsters,
guinea pigs, gerbils,
chipmunks, rats, mice,
other rodents, rabbits
and hares almost never
require antirabies
treatment.
----------------------------------------------------------------------------------------------------------------------------------------------------------------
*/*References 4 and 5.
*During the 10-day holding period, begin treatment with Rabies Vaccine
Adsorbed with or without Rabies Immune Globulin (Human) at first sign of
rabies in a dog or cat that has bitten someone (see Post-Exposure Prophylaxis
below). The symptomatic animal should be killed immediately and tested.
**The animal should be killed and tested as soon as possible. Holding for
observation is not recommended. Discontinue vaccine if immunofluorescence
test results of the animal are negative.
C. POST-EXPOSURE PROPHYLAXIS: Factors to be considered for appropriate post-
exposure antirabies treatment are given in Table 2. (REF. 4,5) These include
the species of animal with which the person has had contact, the circumstances
of the biting incident and vaccination status of the exposing animal, the type
of exposure and the previous rabies immunization history of the person exposed.
Carnivorous wild animals (especially skunks, raccoons and foxes) and bats are
the animals most commonly infected with rabies and the cause of most of the
indigenous cases of human rabies in the United States since 1960. In contrast,
with the exception of woodchucks, rodents (such as squirrels, hamsters, guinea
pigs, gerbils, chipmunks, rats and mice) and lagomorphs (including rabbits and
hares) are rarely found to be infected with rabies and have not been known to
cause human rabies in the United States. The likelihood that a domestic dog or
cat is infected with rabies varies from region to region and depends, in part,
on the vaccination history of the animal. In addition, an unprovoked attack is
more likely than a provoked attack to indicate that an animal is rabid.
Moreover, rabies is transmitted by introducing the virus into open wounds or
mucous membranes. Thus, the likelihood of rabies infection depends, in part, on
whether the exposure occurred by penetrating the skin or by contamination of
mucous membranes by saliva or other potentially infectious material. Physicians
should evaluate each possible exposure to rabies and, if necessary, consult with
their state or local public health officials regarding the need for rabies
prophylaxis.
1. LOCAL TREATMENT OF WOUNDS: Immediate and thorough washing of all bite wounds
and scratches with soap and water is perhaps the most effective measure for
preventing rabies. In experimental animals, simple local wound cleaning has been
shown to reduce markedly the likelihood of rabies. Tetanus prophylaxis and
measures to control bacterial infection should be given as indicated.
2. SPECIFIC TREATMENT: RABIES VACCINE ADSORBED IS NOT INTENDED FOR USE IN
PATIENTS KNOWN TO HAVE CLINICAL MANIFESTATION OF RABIES. The injection schedule
for post-exposure prophylaxis depends on whether the patient has had or has not
had previous vaccination against rabies. FOR PERSONS WHO HAVE NOT PREVIOUSLY
BEEN VACCINATED AGAINST RABIES, the schedule consists of an initial injection IM
of Rabies Immune Globulin (Human) (HRIG), 20 international units per kilogram
body weight in total. If anatomically feasible, up to half the dose of HRIG
should be thoroughly infiltrated around the wound(s) and the remainder should be
administered IM in the gluteal region (for specific instructions for HRIG use,
see the product package insert). The HRIG injection is followed by a series of 5
individual injections of Rabies Vaccine Adsorbed given IM on days 0, 3, 7, 14
and 28. The HRIG and Rabies Vaccine Adsorbed should be given at separate sites
using separate syringes. Post-exposure rabies prophylaxis should begin the same
day exposure occurred or as soon after exposure as possible. The combined use of
HRIG and Rabies Vaccine Adsorbed is recommended for both bite and non- bite
exposures, regardless of the interval between exposure and initiation of
treatment. The sooner treatment is begun after exposure, the better. However,
there have been instances in which the decision to begin treatment was made as
late as 6 months or longer after exposure due to delay in recognition that an
exposure had occurred. Post-exposure antirabies vaccine should always include
administration of both passive antibody and vaccination with the exception of
persons who have previously received complete vaccination regimens (pre-exposure
or post- exposure) with a cell culture vaccine, or persons who have been
vaccinated with other types of vaccines and have had documented rabies antibody
titers. PERSONS WHO HAVE PREVIOUSLY RECEIVED RABIES VACCINATION are given 2 IM
doses of Rabies Vaccine Adsorbed: 1 on day 0 and another on day 3. They should
not be given HRIG.
3. TREATMENT OUTSIDE THE UNITED STATES: If post- exposure prophylaxis is begun
outside the United States with locally produced biologics, it may be desirable
to provide additional treatment when the patient reaches the United States.
State health departments should be contacted for specific advice in each case.
(REF. 4)
CONTRAINDICATIONS:
Rabies Vaccine Adsorbed is contraindicated in persons who have had life-
threatening allergic reactions to previous injections of this vaccine or to
components of this vaccine, including thimerosal. No such reactions have been
seen to date but are theoretically possible since less severe allergic reactions
have been observed. Persons who have experienced non-life-threatening allergic
reactions to Rabies Vaccine Adsorbed may receive additional injections under
appropriate medical supervision, if the indications for vaccination justify the
risk and vaccines are not available to which the patient has not had a reaction.
WARNINGS:
Pre-exposure immunization should be delayed in persons with an acute
intercurrent illness.
Rabies Vaccine Adsorbed should be injected into the deltoid muscle unless the
use of that muscle is contraindicated. As is the case in giving any adsorbed
vaccine, care should be taken to avoid accidentally depositing Rabies Vaccine
Adsorbed in close approximation to a peripheral nerve or in adipose and
subcutaneous tissue.
PRECAUTIONS:
GENERAL: In adults and children, the vaccine should be injected into the
deltoid muscle. In small children, the mid-lateral aspect of the thigh area may
be preferable.
As with the injection of any biologic material that may induce an allergic
reaction, epinephrine injection (1:1,000) should be available for immediate use
should an anaphylactic reaction occur.
This vaccine should be given with caution to persons who are known to be
sensitive to or allergic to monkey proteins. If a patient known to be allergic
to monkey proteins has been exposed to a known rabid animal, and if no other
rabies vaccine is available, then administration of Rabies Vaccine Adsorbed to
the allergic patient should be done under the supervision of a physician
qualified in the management of allergic reactions. Local or mild post-
vaccination reactions are not a contraindication to continuing immunization.
DRUG INTERACTIONS: Immunosuppressive agents, antimalarials and
immunosuppressive diseases can interfere with development of active immunity
after vaccination and may reduce the effectiveness of rabies vaccine.
Immunosuppressive agents should not be given during post-exposure therapy unless
essential for treatment of other conditions. When post-exposure prophylaxis is
given to immunosuppressed persons, it is important that serum be tested for
rabies antibody to ensure that an adequate response occurred.
LABORATORY TESTS: Routine testing for rabies antibody response to vaccination
is not necessary. Experience from clinical trials documented that antibodies can
be detected consistently in serum samples obtained approximately 2 weeks after
the last injection. For immunosuppressed persons see Drug Interactions.
PREGNANCY CATEGORY C: Animal reproduction studies have not been conducted with
Rabies Vaccine Adsorbed. It is also not known whether Rabies Vaccine Adsorbed
can cause fetal harm when administered to a pregnant woman or can affect
reproductive capacity. Rabies Vaccine Adsorbed should be given to a pregnant
woman only if clearly needed.
PEDIATRIC USE: Rabies Vaccine Adsorbed has been administered to children as
young as 6 years old without noticeable difference in effects from its
administration to adults. All children from whom post-vaccination serum was
obtained showed rabies antibody titers greater than 1:5. However, because of the
limited experience with this vaccine in children, special precautions should be
taken for unexpected adverse events.
DRUG INTERACTIONS:
Immunosuppressive agents, antimalarials and immunosuppressive diseases can
interfere with the development of active immunity after vaccination and may
reduce the effectiveness of rabies vaccine. Immunosuppressive agents should not
be given during post-exposure therapy unless essential for treatment of other
conditions. When post-exposure prophylaxis is given to immunosuppressed persons,
it is important that serum be tested for rabies antibody to ensure that an
adequate response occurred.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
Once initiated, rabies prophylaxis should not be interrupted due to mild local
or systemic reactions.
LOCAL: Approximately 65% to 70% of persons given IM injections of Rabies
Vaccine Adsorbed reported subjective mild, transient discomfort localized to the
injection site. In a few, aching of the injected muscle and a mild local
inflammatory reaction consisting of swelling, induration or erythema were
present for 48 hours. These local complaints can usually be successfully treated
with simple analgesics.
SYSTEMIC: Mild, transient constitutional reactions have been reported by 8% to
10% of Rabies Vaccine Adsorbed recipients. These consisted chiefly of headache,
nausea, slight fever or fatigue. Also, serum-sickness-like reactions, some with
arthralgia, suggestive of hypersensitivity to Rabies Vaccine Adsorbed, have been
reported in less than 1% of vaccinees between 7 and 14 days after vaccination.
These hypersensitivity reactions have occurred after booster vaccination, but
have not been seen following primary immunization with Rabies Vaccine Adsorbed.
The occurrence of allergic reactions in patients receiving either Rabies Vaccine
Adsorbed or Human Diploid Cell Rabies Vaccine raises special difficulties for
the managing physician. The use of pre-exposure booster doses of Human Diploid
Cell Rabies Vaccine has been limited by the observation of serum-sickness-like
allergic reactions that occur in approximately 6% of individuals who receive
boosters with that vaccine. (REF. 5) These reactions are thought to be due to
small amounts of human serum albumin that have been rendered allergenic by
betapropiolactone. Human serum albumin is not used in the medium used to grow
the rabies virus for Rabies Vaccine Adsorbed and therefore is not present when
betapropiolactone is added to inactivate the virus. Nevertheless, systemic
allergic reactions have also occurred in some individuals following booster
doses of Rabies Vaccine Adsorbed at a rate of less than 1%. However, it is not
known whether patients who are allergic to Rabies Vaccine Adsorbed are also
allergic to Human Diploid Cell Rabies Vaccine and vice versa. Thus, judgments
must be made regarding whether or not to continue the vaccination schedule and
whether or not to change the vaccines.
OTHER: Neurologic reactions such as those reported to be temporally associated
with the administration of other viral vaccines, including Human Diploid Cell
Rabies Vaccine, for example, allergic peripheral neuritis, encephalomyelitis or
transverse myelitis, have not been reported in recipients of Rabies Vaccine
Adsorbed.
If serious adverse reactions are noted, report them promptly to the
manufacturer: Michigan Department of Public Health, 517-335-8050 during working
hours or 517-335-9030 at other times. Reports may also be submitted directly to
the FDA on form FDA-1639, single copies of which may be obtained from the
Division of Epidemiology and Surveillance (HFN-730), 5600 Fishers Lane,
Rockville, MD 20857.
DOSAGE AND ADMINISTRATION:
Each vial of Rabies Vaccine Adsorbed contains a sufficient volume of vaccine to
enable withdrawing a full dose of 1.0 mL. The vial should be shaken gently
before withdrawing the vaccine to ensure complete suspension of the aluminum
phosphate adjuvant. The vaccine should be given IM. THIS VACCINE IS NOT FOR USE
BY THE ID ROUTE. Before injecting the vaccine, the syringe barrel should be
retracted sufficiently to create a back-pressure to ascertain whether the needle
is in the lumen of a blood vessel.
In adults and children, the site of the injection is the deltoid muscle.
Administration into the buttock is not recommended since experience with other
vaccines has shown that acceptable antibody titers may not be obtained. (REF. 3)
In small children, who may have insufficient deltoid muscle mass, the
anterolateral aspect of the thigh is an acceptable injection site.
PRE-EXPOSURE VACCINATION: Pre-exposure vaccination consists of three 1.0 mL IM
injections of rabies vaccine, 1 each given at 0, 7 and 21 or 28 days. (Also see
Table 1.)
BOOSTER VACCINATION: Booster vaccination consists of a single 1.0 mL IM
injection of vaccine.
POST-EXPOSURE PROPHYLAXIS: Post-exposure prophylaxis for persons NOT previously
vaccinated against rabies consists of an injection of HRIG, 20 international
units per kilogram body weight, and five 1.0 mL injections of Rabies Vaccine
Adsorbed, intramuscularly, 1 each to be given on days 0, 3, 7, 14 and 28. The
amount of HRIG administered should not exceed the recommended amount. Post-
exposure prophylaxis for persons who HAVE been previously vaccinated against
rabies consists of two 1.0 mL IM injections of Rabies Vaccine Adsorbed: 1 at day
0 and the second on day 3. HRIG should not be given. Persons should be
considered to HAVE been immunized previously if they received pre- or post-
exposure prophylaxis with Rabies Vaccine Adsorbed or Human Diploid Cell Rabies
Vaccine or have been documented to have had an adequate antibody response to
Duck Embryo Rabies Vaccine. (Also see Table 2.)
Parenteral drug products should be inspected for particulate matter and
discoloration prior to administration, whenever solution and container permit.
This vaccine should have a light pink color due to the presence of phenol red in
a neutral solution. Do not use vials that are discolored or contain particulate
matter.
REFERENCES:
1. Shill, M., Baynes, R.D., and Miller, S.D.: Fatal Rabies Encephalitis Despite
Appropriate Post-Exposure Prophylaxis. N. Engl. J. Med. 316:1257-1258, 1987.
2. Baer, G.M., and Fishbein, D.B.: Rabies Post- Exposure Prophylaxis. N. Engl.
J. Med. 316:1270-1272, 1987.
3. Centers for Disease Control: Human Rabies Despite Treatment with Rabies
Immune Globulin and Human Diploid Cell Rabies Vaccine--Thailand. MMWR.
36:(November 27) 757-760, 765, 1987.
4. Centers for Disease Control: Rabies Prevention--United States, 1991:
Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR.
40 (No. RR-3): 1-19, 1991.
5. Centers for Disease Control: Rabies Vaccine Adsorbed: A New Rabies Vaccine
for Use in Humans. MMWR. April 1988.
ADDITIONAL REFERENCES
6. Corey, L., and Hattwick, M.A.W.: Treatment of Persons Exposed to Rabies.
JAMA. 232:272-276, 1975.
7. Burgoyne, G.H., Kajiya, K.D., Brown, D.W., and Mitchell, J.R.: Rhesus Diploid
Rabies Vaccine (Adsorbed): A New Rabies Vaccine Using FRhL-2 Cells. J. Infect.
Dis. 152:204-210, 1985.
8. Berlin, B.S., Mitchell, J.R., Burgoyne, G.H., et al.: Rhesus Diploid Rabies
Vaccine (Adsorbed), A New Rabies Vaccine: Results of Initial Clinical Studies of
Pre-Exposure Vaccination. JAMA. 247:1726-1728, 1982.
9. Berlin, B.S., Mitchell, J.R., Burgoyne, G.H., et al.: Rhesus Diploid Rabies
Vaccine (Adsorbed), A New Rabies Vaccine II. Results of Clinical Studies
Simulating Prophylactic Therapy for Rabies Exposure. JAMA. 249:2663-2665, 1983.
10. Bahmanyar, M., Fayaz, A., Nour-Salehi, S., et al.: Successful Protection of
Humans Exposed to Rabies Infection. JAMA. 236:2751-2754, 1976.
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DESCRIPTION:
Rabies Immune Globulin (Human)- BayRab (TM) treated with solvent/detergent is a
sterile solution of antirabies immune globulin for intramuscular administration;
it contains no preservative. BayRab is prepared by cold ethanol fractionation
from the plasma of donors hyperimmunized with rabies vaccine. The immune
globulin is isolated from solubilized Cohn Fraction II. The Fraction II solution
is adjusted to a final concentration of 0.3% tri-n-butyl phosphate (TNBP) and
0.2% sodium cholate. After the addition of solvent (TNBP) and detergent (sodium
cholate), the solution is heated to 30 deg C and maintained at that temperature
for not less than 6 hours. After the viral inactivation step, the reactants are
removed by precipitation, filtration and finally ultrafiltration and
diafiltration. BayRab is formulated as a 15-18% protein solution at a pH of 6.4-
7.2 in 0.21-0.32 M glycine. BayRab is then incubated in the final container for
21-28 days at 20-27 deg C. The product is standardized against the U.S. Standard
Rabies Immune Globulin to contain an average potency value of 150 IU/mL. The
U.S. unit of potency is equivalent to the international unit (IU) for rabies
antibody.
The removal and inactivation of spiked model enveloped and non-enveloped viruses
during the manufacturing process for BayRab has been validated in laboratory
studies. Human Immunodeficiency Virus, Type 1(HIV-1), was chosen as the relevant
virus for blood products: Bovine Viral Diarrhea Virus (BVDV) was chosen to model
Hepatitis C virus; Pseudorabies virus (PRV) was chosen to model Hepatitis B
virus and the Herpes viruses; and Reo virus type 3 (Reo) was chosen to model
non-enveloped viruses and for its resistance to physical and chemical
inactivation. Significant removal of model enveloped and non- enveloped viruses
is achieved at two steps in the Cohn fractionation process leading to the
collection of Cohn Fraction II: the precipitation and removal of Fraction III in
the processing of Fraction II + IIIW suspension to Effluent III and the
filtration step in the processing of Effluent III and Filtrate III. Significant
inactivation of enveloped viruses is achieved at the time if treatment of
solubilized Cohn Fraction II with TNBP/sodium cholate.
ACTIONS/CLINICAL PHARMACOLOGY:
The usefulness of prophylactic rabies antibody in preventing rabies in man when
administered immediately after exposure was dramatically demonstrated in a group
of persons bitten by a rabid wolf in Iran. (REF. 1,2) Similarly, beneficial
results were later reported from the U.S.S.R. (REF. 3) Studies coordinated by
WHO helped determine the optimal conditions under which antirabies serum of
equine origin and rabies vaccine can be used in man. (REF. 4-7) These studies
showed that serum can interfere to a variable extent with the active immunity
induced by the vaccine, but could be minimized by booster doses of vaccine after
the end of the usual dosage series.
Preparation of rabies immune globulin of human origin with adequate potency was
reported by Cabasso et al. (REF. 8) In carefully controlled clinical studies,
this globulin was used in conjunction with rabies vaccine of duck-embryo origin
(DEV). (REF. 8,9) These studies determined that a human globulin dose of 20
IU/kg of rabies antibody, given simultaneously with the first DEV dose, resulted
in amply detectable levels of passive rabies antibody 24 hours after injection
in all recipients. The injections produced minimal, if any, interference with
the subject's endogenous antibody response to DEV.
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RABIVAX
RABIES VACCINE U.S.P.
Sll RABIVAX liquid
DESCRIPTION
Rabies Vaccine U.S.P. (Adsorbed) Sll RABIVAXO is a sterile, cell culture derived vaccine for pre-and-post-exposure prophylaxis in humans. It is prepared with Pitman-Moore strain of rabies virus. The virus is propagated on human diploid cells. The virus is inactivated with p propiolactone. After inactivation the virus is adsorbed onto aluminum phosphate.
COMPOSITION:
Rabies virus (Pitman-Moore strain) adapted, grown on human diploid cells and inactivated by using p propiolactone. Each dose of 1 ml contains: Potency of Rabies antigen^2.5 I.U. Adsorbed onto Aluminium Phosphate AI+'+ not more than 1.25 mg Preservative: Thiomersal 0.01 % Dose: 1 ml by Intramuscular injection
INDICATIONS
A. Rabies prevention in subjects exposed to a risk of contamination This vaccination is particularly recommended for:
-Professional groups exposed to frequent contaminations
-veterinary surgeons including students at veterinary colleges
-technical personnel working with veterinary surgeons.
-laboratory personnel handling material contaminated with rabies virus
-personnel in abbatoirs and knackers yards, taxidermists, animalists
-farmers, gamekeepers, and forestry workers in enzootic areas and naturalists
B, Treatment after certain or_ plausible rabies contamination
-Treatment of subjects bitten by rabid animals or those suspected of being so
-Treatment of contract subject
contraindications
Rabies vaccine adsorbed is contraindicated in persons who have had life threatening allergic reactions to previous injections of this vaccine or to components of this vaccine including thiomersal. When pre-exposure treatment is given, vaccination can be postponed in high fever, acute or chronic disease. In pregnancy benefit risk ratio should be assessed and vaccine can be deferred. When post-exposure treatment is given due to fatal course of rabies, pregnancy is not a contraindication. WARNINGS
In cases of serious contamination, it is recommended by the World Health Organization that a treatment of 20 I.U. per kg. of specific human rabies immune globulin or 40 I.U. per kg of purified rabies serum of animal origin, be started in conjunction on first day of vaccination (DO). In subjects who have received preventive vaccination within a period of one year, and who can prove it by a vaccination certificate, it is recommended that 2 or 3 immunizing doses be given to the severity of the bite.
Do not administer vaccine by intravascular route.
DRUG INTERACTIONS
The corticosteroids and Immunosuppressive treatment may lead to vaccination failure. In these cases, a titration of neutralizing antibodies should be performed. SIDE EFFECTS
Local minor reactions like : Redness and slight induration at the injection site, lasting 24 to 48 hours. Rare febrile reactions nausea, headache, fever, malaise or myalgia may also occur. More marked reactions and swelling are possible. More marked local reactions, an increase In body temperature over 38X lymph node swelling, arthritis, and gastro-intestinal disorders may occur. DOSAGE AND ADMINISTRATION
Rabies vaccine should be injected intramuscularly into the deltoid muscle (In adults and children the anterio-lateral aspect of the thigh is an acceptable injection site). The vaccine vial should be well shaken before use. A. PRE-EXPOSURE IMMUNIZATION
3 injections of 1 ml by intramuscular route on DO. D7. D28, booster 1 year later. Injection can also be given on day 21. Booster injections every 5 years
For countries which follow the WHO recommendations: 3 injections of rabies vaccine of potency at least 2.5 I.U. given on days DO.D7 and D28 (A few days variation is not important) injection every! year later.
B. POST-EXPOSURE IMMUNIZATION
In subjects unvaccinated against rabies, the treatment consists of 5x1 ml injections by the intramuscular route on DO, D3, D7, DI4, D28 after contact with an animal who is rabid or suspected of being so. A booster dose on D90 is optional.
In those previously immunized by complete preventive vaccination: within a year 2 booster injections of 1 ml given by intramuscular route on DO and D3.
More than a year earlier: 3 booster injections of 1 ml given intramuscularly on DO. D3and D7.
According to the degree and severity of bite, in cases of severe bites, 20 I. U. kg body weight of specific rabies immunoglobulin of human origin should be given in conjunction on DO, which will provide protective antibodies immediately.
A. Local treatment of wounds involving possible exposure to Rabies recommended in all exposures.
First aid or local treatment consists of immediate thorough flushing and washing of the wound with water, or soap and water followed by the application of 70% alcohol (700ml per litre) or tincture of iodine. Medical care may then consists of the instillation of a rabies immunoglobulin (after skin testing, if necessary) onto the depth of the-wound should not be sutured, but if suturing is necessary then it is essential that it be preceded by the administration of rabies immunoglobulin {antiserum) as above.
STORAGE
Rabies vaccine should be stored between 2'C and 8'C. Do not freeze, Discard if the product has been frozen.
PRESENTATION
Sll RABIVAX* is available as vial containing
1 ml -1 dose carton plus sterile disposable syringe and needle.
GUIDE FOR POST EXPOSURE TREATMENT
Category Type of contact with suspect or confirmed Rabid domestic/wild3 animal, or animal unavailable for observation Recommended treatment
I Touching or feeding of animals. Licks on intact skin None, if reliable case history is available
II Nibbling of uncovered skin, Minor scratches or abrasions without bleeding. Licks on broken skin Administer vaccine immediately b Stop treatment if animal remains healthy throughout an observation period c of 1 0days or if animal is killed humanely and found to be negative for rabies by appropriate laboratory techniques
III Single or multiple transderrmal bites or scratches. Contamination of mucous membrane with saliva (i.e. Licks) Administer rabies immunoglobulin and vaccine immediately h Stop treatment if animal remains healthy throughout an observation period of 10 days or if animal is killed humanely and found to be negative for rabies by appropriate laboratory techniques.
a) Exposure to rodents, rabbits and hares seldom, if ever, requires specific anti-rabies treatment.
b) If an apparently healthy dog or cat in or from a low-risk area is placed under observation, the situation may warrant delaying initiation of treatment.
c) This observation period applies only to dogs and cats. Except in the case of threatened or endangered species, other domestic and wild animals suspected as rabid should be killed humanely and their tissues examined using appropriate laboratory techniques.
In case of Rabies vaccines, the HDC vaccine has been recognized as the 'Gold Standard1 the world over. Even the WHO in its position paper of 2002 (on Rabies) mentions HDC rabies vaccine as the Gold Standard. The HDC vaccine was available in India but phased out due to it's high cost.
After years of Research & Development, Serum Institute of India Ltd, Pune is proud to introduce the indigenously manufactured HDC rabies vaccine (liquid, adsorbed) on the Pitman Moore strain, used world-wide i.e. RABIVAX
Rabivax is a unique rabies vaccine in the world. It is the only HDC rabies vaccine available in the adsorbed form, which makes it a Ready-to-use vaccine, as there is no dissolution step. The details of its features: Features
• Cultured on Human Diploid Cells
• Contains the acclaimed Pitman Moore strain
Unique Ready-to-use Liquid vaccine
(adsorbed) -;
• Highly Stable: Potency maintained even when stored at 37 °C for 4 weeks
• Free of antibiotics Clinical Features
The several clinical studies that
been conducted have shown that clinicians can expect the following from RABIVAX: High Efficacy
• Excellent immunogenicity and efficacy
• 100% seroconversion by day 14
High antibody titers, well over the minimum protective level
• Level of antibodies unaffected by use of RIG
High Safety
Safe in individuals allergic to other cell culture vaccine components
• egg proteins • avian proteins
. neomycin, chlortetracycline, streptomycin, polymyxin B
Low reactogenecity
. Mild ADRs reported in only 1.43% vaccinees (n = 1608 patients, doses=4180)
• No Type III hypersensitivity reactions as reported with
older imported HOC vaccine Advantages of HDCV vaccines
• It is known to be the safest vaccine, free of
complications. (Davidson's Principles & Practice of Medicine, 19th ed, 2002)
• The Human Diploid Cell Rabies Vaccine is regarded as the Gold Standard for rabies vaccines (WHO Weekly Epidemiological Record, No. 14, 5th April 2002)
• The Human Diploid Cell Rabies vaccines have been given to more than 1.5 million people world wide (WHO Weekly Epidemiological Record, No. 14, 5th April 2002)
• Its protective efficacy in situations of heavy exposure has been shown in the Islamic Republic of Iran where none of 45 persons who received post exposure treatment with this vaccine developed rabies following severe bites by rabid dogs or wolves (WHO Weekly Epidemiological Record, No. 14, 5th April 2002)
. The use of RIG has no effect on the level of antibody titer produced. (Vodopija, et al Vaccine Vol. 15 No. 5, 1997)
Stability:
RABIVAX is stable during the shelf life of 2 years at
recommended Storage temperature of 2-8° C and at 37°C for
4 weeks (accelerated and degradation studies)
Composition of Vaccine:
Rabies Virus (Pitman Moore strain) adapted, grown on human
diploid cells and inactivated by using p-Propiolactone
Each dose of 1 ml contains:
Potency of Rabies antigen > 2.5 IU Adsorbed onto Aluminium
Phosphate, Al+++not more than 1.25mg
Preservative: Thiomersal 0.01 %
Dose: 1 ml by intramuscular injection
Preamble
Several studies done with HOC Rabies vaccine have shown excellent immunogenicity profile. The current new and novel HOC Rabies vaccine (liquid adsorbed), RABIVAX was assessed for safety and efficacy by conducting clinical trials in Indian population utilizing pre-exposure and post-exposure regimens. The clinical studies were conducted as per Good Clinical Practice Guidelines and in accordance with the Declaration of Helsinki. Following successful completion of Phase III clinical trials the product was licensed for use in India. Post-marketing surveillance has been conducted on usage of around 5000 doses in different categories of animal bites. More than 229,000 doses of RABIVAX have been marketed in India.
A summary of the Clinical studies conducted with Human Diploid Cell Rabies Vaccine (RABIVAX, Liquid Adsorbed), Pitman-Moore Strain on MRC-5 Cell line follows
1. Phase I Clinical trial- A Preliminary Study to assess the Safety of Human Diploid Cell Rabies Vaccine (Liquid-adsorbed) Pitman Moore Strain manufactured by SIIL, Pune.
Study Site :
Anti Rabies Unit. Government Medical College, Amritsar
This comparative clinical study was conducted on 20 normal healthy volunteers (10 in each group) receiving HOC (liquid, SIIL) and HOC (lyophilized, Pasteur Merieux) to assess and compare the safety of both the vaccines. The vaccine was given on days 0, 7 and 21 (Pre-exposure regimen) in a dose of 1 ml in the deltoid region. Blood samples were drawn on days 0, 14 and 28 to assess the Rabies Neutralizing Antibody (RnAb) titres by RFFIT at Pasteur Institute Of India, Coonoor (A WHO collaborating Centerfor Rabies in India). The adverse events observed in either vaccine groups are given below:-
These ADEs were observed on the first day, post-immunization which last for 1 -2 days and thereafter resolved on their own, thus, proving the safety of RABIVAX (liquid-adsorbed). Rabies Neutralizing Antibody (RnAb) Titres were comparable for both the groups, being 24.25 lU/ml for RABIVAXand 22.62 ID/ml for HOC, PM.
2. Phase III Clinical trial- A Preliminary Study to assess the Safety and Immunogenicity of HOC Rabies Vaccine (Liquid) Pitman Moore Strain manufactured bySIIL, Pune.
Study Site: Rabies Surveillance Unit.
Kempegowda Institute Of Medical Sciences, Bangalore
This comparative clinical study was conducted on 43 subjects of animal bite receiving HOC (liquid-adsorbed, SIIL)and HOC (Lyophilized, MIRV, France) to assess and compare the safety and immunogenicity of both the vaccines. 29 subjects received HOC, SIIL and 14 subjects received HOC, MIRV, France. The vaccine was given on daysO, 3, 7, 14 and 28 (Post-exposure regimen) in a dose of 1 ml in the deltoid region. Blood samples were drawn on days 0, 14, 28 and 90 to assess the Rabies Neutralizing Antibody (RnAb) titres by RFFIT at Pasteur Institute Of India, Coonoor.
The passive administration of Pasteur Anti-Rabies Serum in Class III / High risk exposure subjects did not interfere with the immunogenicity of either vaccine. None of the subjects in either group, showed any adverse reactions, thus signifying excellent tolerability of the vaccine. It is concluded that RABIVAX manufactured by SIIL, Pune is well tolerated, immunologically highly efficacious and gives more sustained immune response (higher GMTs on day 90 as compared to HOC, PM (MIRV)
3. Phase III Clinical trial- A Phase III Open, Comparative Clinical Trial to assess the efficacy of Human Diploid Cell Rabies Vaccine (Liquid-Adsorbed) manufactured by SIIL, Pune with standard commercially available Rabies Vaccine.
Study Site:
Anti Rabies Unit, Government Medical College, Amritsar
This comparative clinical study was conducted on 38 subjects of animal bite receiving HOC (liquid-adsorbed, SIIL) and HDC (Lyophilized, MIRV, France) to assess and compare the safety and efficacy of both the vaccines. 24 subjects received. HDC, SIIL and 15 subjects received HDC, MIRV, France. The vaccine was given on days 0, 3, 7, 14 and 28 (Post-exposure regimen) in a dose of 1 ml in the deltoid region. Blood samples were drawn on days 0, 14, 28 and 90 to assess the Rabies Neutralizing Antibody (RnAb) titres by RFFIT at Pasteur Institute Of India, Coonoor (A WHO collaborating Centre for Rabies in India).
ERIG was given to all Class III bite subjects. Percentage of patients protected with titres > 0.5 lU/ml on day 14, 28 and 90 was 100% with both the vaccines. Based on these results, the Investigators conclude that HDC Rabies Vaccine (RABIVAX liquid-adsorbed)-Pitman Moore strain manufactured by SIIL, Pune is well tolerated, safe and efficacious with comparable Rabies Neutralizing Antibody Titres (RnAb) to HDC, MIRV, a gold standard for Rabies Immunization.
4. Phase IV Clinical trial- A Phase IV Study to assess the immunogenicity and reactogenicity of HDC Rabies Vaccine (liquid-adsorbed), RABIVAX manufactured by SIIL, Pune
Study Site:
Rabies Surveillance Unit, Kempegowda Institute Of Medical
Sciences, Bangalore
This clinical study was conducted on 145 subjects to assess the immunogenicity and reactogenicity in subjects with animal bite who received HDC (liquid-adsorbed SIIL) Rabies Vaccine, RABIVAX. The vaccine was given on days 0, 3,7, 14 and 28 (Post-exposure regimen) in a dose of 1 ml in the deltoid region. Blood samples were drawn on days 0, 14, 28 and 90 to assess the Rabies Neutralizing Antibody (RnAb) titres by RFFIT at Pasteur Institute Of India, Coonoor (A WHO collaborating Centre for Rabies in India).
No serious adverse event attributable to the vaccine occurred in any of the animal bite subjects thus concluding that RABIVAX indigenously manufactured by Serum Institute Of India Ltd., Pune is a safe and immunogenic vaccine for treatment of animal bites.
5. Phase IV Study to assess the reactogenicity of HOC
Rabies Vaccine (liquid-adsorbed), RABIVAX manufactured by
SIIL, Pune
Study Site :
Conducted at different locations in India
Post marketing surveillance data was obtained on 1608 animal bite subjects of either sex aged 4-60 years who received 4180 doses of RABIVAX in a dose of 1 ml by the intramuscular route. This Phase IV study was conducted to assess the reactogenicity of RABIVAX , HDC Rabies Vaccine (liquid-adsorbed). The salient findings of this study confirm the excellent tolerability profile as evidenced by the graphical representation below:-
Out of 4180 doses of vaccine used in 1608 subjects, adverse events were observed in only 23 (1.43%) subjects which included pain at injection site, induration both of which lasted for 1 -2 days and subsided on its own. Fever was observed in 2 subjects which subsided with concomitant medication. No other serious adverse event was observed in any of the animal bite victims, post vaccination, thus proving the excellent safety