30 Years of Rabies Vaccination With Rabipur - A Summary of Clinical Data and Global Experience - Expert Review of Vaccines - Vol 14, No 3

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Vaccine Profile
30 years of rabies vaccination with Rabipur:

a summary of clinical data and global
experience
Alexandra Giesen , Dieter Gniel & Claudius Malerczyk
Pages 351-367 | Published online: 16 Feb 2015
 Download citation  https://doi.org/10.1586/14760584.2015.1011134
Abstract
Rabies poses a threat to more than 3.3 billion people worldwide and is estimated to cause
about 60,000 deaths a year. However, according to the WHO, it is still one of the most
neglected diseases in developing countries. Human rabies vaccinations are critical
components of pre-exposure and post-exposure prophylaxis. Rabipur®, the first purified
chick embryo cell-culture vaccine, was licensed in Germany in 1984, and later in more than
60 countries worldwide. The immunogenicity, efficacy and safety of Rabipur have been
assessed in numerous clinical trials in pre- and post-exposure regimens, using both
intramuscular and intradermal routes of administration. The trial populations have involved
adults and children, including healthy volunteers and individuals bitten by laboratory-proven
rabid animals, malnourished children and immunocompromised individuals. Extensive,
worldwide clinical experience with Rabipur over the past 30 years has shown the vaccine to
In this article 
be immunogenic, effective and generally well tolerated.
https://www.tandfonline.com/doi/full/10.1586/14760584.2015.1011134 1/34
10/15/2018 30 years of rabies vaccination with Rabipur: a summary of clinical data and global experience: Expert Review of Vaccines: Vol 14, …
be u oge c, e ect e a d ge e a y e to e ated.
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Keywords: cell-culture vaccine, efficacy, exposure, immunogenicity, intradermal, intramuscular, post-
exposure prophylaxis, pre-exposure
 Reprints & Permissions prophylaxis, purified chick embryo cell
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vaccine, rabies, Rabipur®, safety, vaccine
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Erratum
Rabies is a zoonotic viral disease of mammals that is transmitted from animals to humans,
although there have been exceptional reported cases of direct human-to-human
transmission and indirect transmission via infected transplants  [1–3]. The rabies virus is a
member of the genus Lyssavirus, which belongs to the family of Rhabdoviridae. The
incubation period is typically 1–3 months, but can vary from a few days to more than 1 year
 [1,4]. Cases of up to 6 years incubation period have been discussed  [5]. Initial
symptoms are usually nonspecific, including fever and headache. Unfortunately, as the virus
enters into the CNS an acute encephalitis or meningoencephalitis develops. This can result in
various forms of neurological and psychological manifestations, usually followed by paralysis
and coma, and finally death  [1]. Once clinical symptoms of the disease develop, rabies is
nearly always fatal  [6].
Rabies is known to be present on all continents (except Antarctica) and infects both wild and
domestic animals  [7]. This disease poses a potential threat to more than 3.3 billion people
and is estimated to cause about 60,000 deaths each year  [7,8]. Given that reliable data are
unavailable in many regions due to under or no reporting and inadequate surveillance, it is
estimated that in some countries the incidence of rabies could be as much as 15-times
higher than that of official reports  [1,9]. According to the WHO, rabies is still one of the
most neglected diseases in developing countries  [10]. The majority of human fatalities
occur in Asia and Africa where rabies is mainly transmitted by dog bites. In contrast, human
rabies in Europe and North America is rare; countries in these regions are either free of
terrestrial or canine rabies, but the virus circulates in other mammalian animal reservoirs,
including bats. In Latin America and the Caribbean, cases of human rabies transmitted by
dogs have been significantly reduced in the past 20 years  [1,8].
While in countries where rabies is endemic, all people are at risk of being exposed. Children
in these countries have the highest risk due to several behavioral factors. Examples include
children’s attraction toward animals, lack of awareness of potential dangers and reluctance
to report bites or scratches. Moreover, their small stature makes them more susceptible to
be bitten in the face, head and hand, which decreases the incubation period of the rabies
be b tte t e ace, ead a d a d, c dec eases t e cubat o pe od o t e ab es
virusupon infection.
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& data 30 and 50%
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reported to be provided to children  [1,11].

Rabies prevention and control consists of different methods including wild and domestic
animal vaccination programs, animal birth control, responsible pet ownership, and rabies
education and awareness. Human rabies vaccination is one of the most important elements
of preventing rabies in humans. Officially recommended pre-exposure prophylaxis (PrEP)
and PEP regimens should be followed before potential or after actual exposure, respectively
 [1,8].
Rabies vaccines – historical development
Originally, rabies vaccines were derived from animal nerve or brain tissue, so-called nerve
tissue vaccines (NTVs). Nowadays, rabies vaccines are mostly cell-culture and embryonated
egg-based vaccines (jointly referred to as CCEEVs) and only a few countries still use NTVs
 [8]. The first reported rabies vaccination with an NTV was in 1885 when Louis Pasteur
successfully treated a young boy who had been severely bitten by a rabid dog with a series
of vaccinations consisting of a spinal cord suspension of increasing virulence derived from
rabid rabbits  [12]. Improvements were later made to the vaccine’s safety by inactivating
the virus with phenol. However, there were still severe side effects following administration
of NTVs, including some cases of paralysis and even death. A major factor is due to patient
hypersensitivity to myelin  [12,13]. Nerve tissue-derived vaccines produced from brains of
suckling animals were later used as these contain smaller amounts of myelin  [14]. A
modified preparation produced with suckling mouse brain tissue is still used in a small
number of Latin American countries, and NTVs from virus-infected goat or sheep brain
tissue are still utilized in a few countries in Asia and Africa  [15]. However, as NTVs can
induce severe adverse reactions and are less immunogenic than CCEEVs, the WHO does not
recommend the production and use of rabies NTVs  [8,16].
Rabies vaccine production later focused on finding sources of virus propagation in materials
free of neural tissue  [17]. This led to the development of embryonated egg-based and cell-
culture-based vaccines. For embryonated duck egg-based rabies vaccine, the complete
embryo is utilized for virus propagation. In contrast, cell-culture-based vaccines contain the
rabies virus that has been propagated in cell substrates (e.g., primary hamster kidney cells,
human diploid cells, chick embryo cells or Vero cells)  [8,18–21]. Research also addressed
which viral strains should be used. Investigations in humans using low-egg-passage (LEP)
which viral strains should be used. Investigations in humans using low egg passage (LEP)

Fluryvirus showedthat
Full Article the& Flury
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the immunization of humans against rabies – although at that time (the early 1950s) the
vaccine was not highly immunogenic  [22]. Experiments with a high-egg-passage Flury
vaccine resulted in better immunogenicity, but were still inferior to NTVs  [23]. An
inactivated duck embryo virus vaccine appeared to be more promising, but its immunizing
potency was again not as high as that of NTVs  [17].
In the late 1950s, work began on cultures of human fetal fibroblasts, which were diploid cells
that had a finite lifetime. Fetal fibroblasts were soon shown to be susceptible to human
viruses and free of latent viruses  [24]. By the early 1960s, the highly immunogenic human
diploid cell line WI-38 was being used for rabies virus propagation  [24,25]. With some
modifications (including a switch to the MRC-5 cell line), the resulting rabies vaccine
produced using human diploid cells vaccine (HDCV) had a better tolerability profile and
induced a far greater immune response in animals and humans than any other vaccine of
that time  [25–27]. Indeed, Garner and colleagues reported that in their clinical experience,
HDCV was associated with less severe and persistent local inflammation, lymphadenopathy,
headaches and fever than the duck embryo virus vaccine  [28]. Human diploid cells vaccine
was first licensed for pre- and post-exposure immunization in Europe in 1976 and in the USA
in 1980 and is still available now  [27].
Large-scale production of rabies virus in human diploid cell strains is a complex process with
a low virus yield in comparison to other cell systems. It results in high production costs and a
limited output of vaccine for HDCV  [29]. Over subsequent years, a series of different
vaccines have been developed with similar immunogenicity to HDCV  [12]. Licensed in
1985, a purified Vero cell rabies vaccine (PVRV) has comparable immunogenicity to HDCV
with the advantages of a better safety profile  [30].
Investigations into a purified chick embryo cell-culture vaccine (PCECV) for rabies started in
the late 1970s in Marburg, Germany  [28]. In the 1980s, an immunogenic PCECV containing
inactivated rabies virus (LEP Flury strain) was developed. In a series of animal laboratory
tests, PCECV showed comparable immunogenicity and tolerability to that of HDCV  [29]. In
human studies, PCECV induced similar immunogenicity to HDCV  [31–34]. The purified
chick embryo cell-culture vaccine was subsequently licensed in Germany in 1984 as Rabipur®
(Novartis Vaccines). The availability of HDCV, PVRV and PCECV (Rabipur) has enabled dosing
schedules to be vastly reduced and side effects minimized compared with NTVs  [35].
Based on these cell culture production platforms, recently other rabies vaccines have been
developed. Some of them are using different virus strains  [36–38].
de e oped. So e o t e a e us g d e e t us st a s  [36 38].
 

Purified chick embryo cell-culture vaccine – Rabipur
Rabipur is produced using Flury LEP rabies virus strain grown in a culture of primary chick
embryo fibroblast cells using specific pathogen-free eggs in compliance with current
applicable pharmacopeia and with WHO requirements. The Flury LEP rabies virus is
inactivated with β-propiolactone, purified via continuous density-gradient centrifugation,
resulting in a highly concentrated formulation stabilized with polygeline (a processed gelatin
product), and then lyophilized  [39]. Rabipur is produced in two WHO pre-qualified
manufacturing facilities: Marburg, Germany and Ankleshwar, India  [40]. In Marburg,
Germany, a new state-of-the-art manufacturing facility for Rabipur has been approved as of
2014. Batches of Rabipur from the two sites have been shown to be clinically comparable:
noninferiority in immunogenicity and tolerability of the vaccine produced in India to the
vaccine produced in Germany has been demonstrated  [41,42]. Additionally, all batches
compared reach or exceed the minimum potency of ≥2.5 international units per single
intramuscular (IM) dose, as specified by the WHO and approved by regulatory authorities
 [8]. PCECV has been found to have 1000-fold lower concentration (0.024 mg/dose) of
human serum albumin, which is a stabilizer and a considerable component in most vaccines,
compared to PVRV, HDVC and primary hamster kidney vaccines  [43]. Moreover, tested
batches of PCECV were shown to contain Flury LEP rabies virus strain with no deviations
from published genetic sequences  [43]. PCECV is marketed globally as Rabipur, with a few
exceptions: in South Africa and Namibia it is marketed as Rabipor (licensed in 2000) and in
the USA and Canada as RabAvert® (licensed in 1997 and 2003, respectively). Throughout this
manuscript, PCECV will be referred to as Rabipur.
Vaccination regimens
Rabies differs from many other infectious diseases in that, despite following exposure to the
infectious agent, clinical manifestation of the disease may be prevented through timely
immunization (in adherence with WHO protocols) as long as clinical symptoms have not
developed  [8,44]. Thus, both PEP and PrEP regimens are effective in immunizing against
rabies  [45].
Post-exposure prophylaxis
The key immunological objective of PEP is to neutralize and destroy the rabies virus  
inoculated in the victim’s body immediately following exposure so that clinical manifestation
of rabies does not develop. PEP has three main components: wound treatment, vaccine
administration and rabies immunoglobulin (RIG) administration, if indicated  [8,44]. The
WHO recommendations for PEP depend on the type of contact with the suspected rabid
animal and the vaccination status of the individual based on three categories of risk and
exposure (I-III). Definition of categories of exposure and the use of rabies biologicals are as
follows:
Category I is insignificant or no exposure to the animal and therefore requires no

prophylaxis;
Category II is minor scratches or abrasions without bleeding and requires vaccine; and
Category III is transdermal bite or scratches or contamination of mucous membrane or

any exposure to bats, which would require use of RIG plus vaccine  [8,44].
In deploying PEP, the immunization schedule should begin as soon as possible following
exposure and must be followed exactly as recommended, regardless of when the patient
comes in for treatment after the initial contact. In individuals who have not been vaccinated
with the rabies vaccine or individuals with uncertain immune status, Rabipur is administered
via IM injection using the Essen five-dose regimen (one dose on Days 0, 3, 7, 14 and 28) or
the Zagreb four-dose regimen (two doses on Day 0, followed by one dose on Days 7 and 21).
Recently, Advisory Committee on Immunization Practices and WHO have amended their PEP
recommendations to reduce the Essen five-dose regimen to four doses (one dose on Days 0,
3, 7 and 14). This shortened regimen may be used as an alternative for healthy, fully immune
competent, exposed people provided they receive wound care plus RIG in category III as well
as in category II exposures and a WHO-prequalified rabies vaccine  [8,46]. This, however,
until today has not been reflected in the labels of any rabies vaccine. In countries where the
intradermal (ID) route of administration has been endorsed by national regulatory
authorities, the WHO recommends the ID 2-site regimen (updated Thai Red Cross; two doses
of 0.1 ml ID at two different lymphatic drainage sites on Days 0, 3, 7 and 28)  [8,16].
Pre-exposure prophylaxis
PrEP simplifies post-exposure care by eliminating the need for RIG and reducing the number
of doses of vaccine needed for immediate post-exposure immunization. Individuals who
have previously been vaccinated with a rabies vaccine will only need two doses of Rabipur
for PEP (given on Days 0 and 3) as soon as possible after exposure. For PrEP, immunization
o (g e o ays 0 a d 3) as soo as poss b e a te e posu e. o , u at o
consists ofArticle
 Full a 3-dose IM regimen
 Figures & data ofRabipur (administered
References  Citations on
Days 0, 7 and 21 or 28) into a
Metrics

deltoid muscle (anterolateral region of the thigh in small children). The three-dose regimen
can also be administered ID, in countries where ID route of administration is endorsed by
national regulatory authorities  [8,45].
Rabipur clinical trials
The immunogenicity, efficacy and safety of Rabipur have been assessed in more than 50
clinical trials since 1983 in both PEP and PrEP regimens, using IM as well as ID
administration. The trial populations have comprised of adults and children aged 12 months
and older. Subjects included healthy individuals, individuals bitten by suspect or laboratory-
proven rabid animals, malnourished children and immunocompromised persons.
Summaries and overviews of relevant clinical trial results are provided in Tables 1–6, and
individual trials and published case studies are provided exemplarily in detail in the review
text.
Table 6. Summary of Rabipur efficacy following PEP

administration. 
CSV Display Table
Table 1. Summary of Rabipur intramuscular PEP and PrEP

immunogenicity and safety studies in adults. 
CSV Display Table
Table 2. Summary of Rabipur intradermal PEP and PrEP

immunogenicity studies in adults. 
CSV Display Table
Table 3 Rabipur PEP and PrEP immunogenicity and safety

https://www.tandfonline.com/doi/full/10.1586/14760584.2015.1011134
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
Table 3. Rabipur PEP and PrEP immunogenicity and safety
studies in children.
 Full Article  Figures & data  References  Citations  Metrics  

CSV Display Table
Table 4. Rabipur immunogenicity in HIV-infected individuals.
CSV Display Table


Table 5. Rabipur PrEP immunogenicity following a booster
dose in adults and children. 
CSV Display Table
At the time of the vaccine development, a PEP six-dose Essen regimen was officially
recommended by the WHO for all cell-culture rabies vaccines. Consequently, Rabipur was
initially assessed in clinical trials with a six 1.0 ml/dose IM Essen regimen for PEP and was
licensed as such. According to WHO guidelines, the PEP six-dose Essen regimen produced an
adequate antibody response (specific antibody level of ≥0.5 IU/ml)  [8,44,45]. Alternatively,
the Zagreb regimen was developed with an abbreviated schedule (2-1-1) of two doses on Day
0 and one dose on Days 7 and 21. Over time, the sixth dose of the Essen regimen on Day 90
became optional and, in 1992, the WHO published new guidelines that recommended a five-
dose Essen regimen (without the dose on Day 90) for which Rabipur was later indicated
 [47].
Immunogenicity in PEP & PrEP regimens
Rabipur has been investigated extensively in PEP and simulated PEP regimens in humans
and has a well-established immunogenicity and tolerability profile for both the Essen and
Zagreb regimens. An overview and summary of the relevant clinical trials investigating the
immunogenicity of Rabipur in PEP and PrEP IM regimens is provided in Table 1.
A pivotal immunogenicity study assessed several vaccination regimens in 88 healthy

volunteers; 15 volunteers received Rabipur in a simulated PEP six-dose Essen regimen (a
single 1.0 ml IM dose on Days 0, 3, 7, 14, 30 and 90); another 14 volunteers received Rabipur
in the PEP five-dose Essen regimen (a single 1.0 ml IM dose on Days 0, 3, 7, 14 and 30).
t e e dose sse eg e (a s g e .0 dose o ays 0, 3, , a d 30).
Rabies virus
 Full neutralizing
Article  Figuresantibody
& data (RVNA) concentration
References  Citationsof ≥0.5 IU/ml was achieved in all
 Metrics

subjects by Day 14, which has been well established as an adequate antibody response after
vaccination  [48]. Volunteers noted the following reactions to the vaccine: general systemic
reactions (31.2%); local adverse reactions – mostly mild (56.5%); moderate or severe general
reactions, including fatigue, headache and dizziness (15.1%); and moderate or severe local
reactions including pain, induration or redness (16.4%).
The immunogenicity of Rabipur when administered using the WHO-recommended Zagreb

regimen has been demonstrated in several studies. In one trial, 32 individuals were
randomly assigned to receive Rabipur and 50 received PVRV with two doses on Day 0 and a
single dose on Days 7 and 21. All subjects achieved RVNA concentrations ≥0.5 IU/ml within
14 days of initial vaccination and showed no significant difference in the immune response
between Rabipur and PVRV  [49]. These findings support those of others where
administration of Rabipur IM using the Zagreb regimen evoked a rapid and high-titer
antibody response, peaking at Day 14  [32].
Historically, the simultaneous administration of RIG together with rabies vaccines for PEP
raised discussion on possible interference of RIG on the patient’s own active immune
response to the vaccine. A study using human rabies immunoglobulin at the recommended
concentration of 20 IU/kg observed partial interference with the initial active development of
RVNA when administered concomitantly with different types of rabies vaccines applied by
the Zagreb regimen  [50]. When Rabipur was administered in different IM and ID regimens
for PEP simultaneously with either equine rabies immunoglobulin or human rabies
immunoglobulin, initial effects on antibody concentrations were observed in some instances.
However, none of this interference was clinically relevant as RVNA concentrations were
always above the adequate level of 0.5 IU/ml  [51–55].
Rabipur PrEP regimens have been shown to be immunogenic and well tolerated when
administered in humans (Table 1). In a pivotal PrEP study in healthy adults, Rabipur was
given in a three-dose series and followed by a 2-year booster. Vaccination with Rabipur via
an IM or ID regimen resulted in adequate immune response by Day 28, which was sustained
at Day 365  [33]. Comparable results were found in a similar study comparing Rabipur with
HDCV  [34].
Immunogenicity following ID administration
The standard route of administration of Rabipur is IM injection into the deltoid muscle of
adults or the anterolateral region of the thigh in small children  [56]. However, Rabipur
adu ts o t e a te o ate a eg o o t e t g s a c d e  [56]. o e e , ab pu

may be administered
 Full ID in&countries
Article  Figures where thisroute
data  References is endorsed
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authorities  [8]. ID administration is a more economic and antigen-saving alternative to IM

administration as it requires 0.1 ml of vaccine per ID dose, in contrast to 1.0 ml per IM dose
 [8]. In PrEP, Rabipur induces slightly lower levels of RVNA when administered ID compared
with IM  [33]. However, for PEP regimens, RVNA levels following ID and IM administration
of Rabipur are comparable  [52].
The immunogenicity of 0.1 ml Rabipur for ID administration has been well established in
clinical trials (Table 2). A study of 211 patients with WHO category II or III rabies exposure in
Thailand was designed to assess whether Rabipur for ID PEP treatment could effectively be
reduced to 0.1 ml per site. Geometric mean RVNA concentrations on Day 14 after Rabipur ID
(0.1 ml at two sites on Days 0, 3 and 7; one site on Days 30 and 90) were noninferior to
patients who received IM Rabipur (1.0 ml on Days 0, 3, 7, 14, 30 and 90) and were ≥0.5 IU/ml
 [52]. This study employed the Thai Red Cross regimen, which was the former official WHO-
endorsed ID regimen. However, over the years, the dosing schedule for ID administration
has evolved as evidence from clinical trials has become available. The WHO now
recommends the updated Thai Red Cross 2-site regimen as the most cost–effective and
widely used ID regimen: 0.1 ml at two different ID sites on Days 0, 3, 7 and 28  [8].
The WHO-defined minimum vaccine potency of 2.5 IU per IM dose has been established as
effective for use in ID administration as well  [51]. A study by Beran and colleagues
investigated whether the 1.0-ml dose of Rabipur for IM administration was still sufficient to
induce an adequate antibody response after a several-fold dilution and following 0.1 ml ID
administration. The study showed that an adequate RVNA response (≥0.5 IU/ml) was elicited
and maintained when Rabipur was administered via the ID route of administration in the
Thai Red Cross 2-site regimen. These data confirm that the WHO-recommended minimum
potency of 2.5 IU for IM administration is adequate also for the 0.1 ml ID dosing regimen
 [51].
Immunogenicity in children
Children in rabies endemic countries are at particular high risk due to their attraction toward
animals, lack of awareness of potential dangers, potential reluctance to report bites or
scratches and their small stature (making them more susceptible to face, head and hand
bites from animals, which decreases the incubation period). Exposure to the rabies virus
occurs disproportionately in children: on average, 40% of PEP is administered to children
aged 5–14 years  [1]. A number of clinical trials have demonstrated Rabipur to be
immunogenic with an acceptable safety profile in children for both PEP and PrEP (Table 3).
immunogenic with an acceptable safety profile in children for both PEP and PrEP (Table 3).
 
A study in children (n = 11) aged 2–15 years who had single IM doses of Rabipur (1.0 ml) on
Days0,Reprints
7 and 28 & Permissions  PDF
for PrEP showed RVNA concentrations ≥0.5 IU/ml by Day 14. No serious
adverse events (SAEs) were reported after vaccination  [57]. Another study (n = 175)
comparing three IM doses of Rabipur (reconstituted in 1.0 ml or 0.5 ml diluent) or PVRV with
single doses on Days 0, 7 and 28 for PrEP in children aged 6–13 years demonstrated that
RVNA concentrations were ≥0.5 IU/ml by Day 49  [58]. Similar findings have been observed
in children aged 12–18 months receiving IM or ID Rabipur (1.0 or 0.1 ml, respectively) on
Days 0,7 and 28 for PrEP, with concomitant administration of Japanese encephalitis vaccine
 [59]. Rabipur has also demonstrated immunogenicity in older children when administered
by ID injection for PrEP  [56,60]. Rabipur is generally well tolerated in children; reported
typical adverse reactions in clinical trials included fever, tenderness, and pain and redness at
the injection site. No serious adverse reaction related to the vaccine occurred  [57,61–64].
A PEP study assessing Rabipur immunogenicity was carried out in children bitten by either
confirmed or suspected rabid animals (mainly dogs, followed by monkeys, cats and
mongoose). Two hundred and seventy one children aged 1–13 years received PEP on Days 0,
3, 7, 14, 30 and 90. The serological response was adequate, with all children demonstrating
RVNA concentration of ≥0.5 IU/ml with a maximum immune response measured 10–15 days
after the last vaccination. The vaccine was well tolerated and no failures were observed
 [65].
The anamnestic response to simulated post-exposure booster doses of Rabipur has also
been demonstrated in children aged 5–8 years at the time of primary vaccination. Two
booster doses (Days 0 and 3) of Rabipur were administered ID 1, 3 or 5 years after three
primary vaccination doses and resulted in adequate RVNA concentrations (≥0.5 IU/ml) in all
children (n = 312) by Day 14 after booster  [61].
A clinical case study reported on the vaccination of a newborn baby with Rabipur after her
mother developed clinical rabies during pregnancy following a dog bite 3 months prior to
giving birth. A healthy female baby was delivered (gestational age 40 weeks), following which
the baby received a total of five doses of Rabipur: 1.0 ml IM at birth and a four-dose series
(Days 3, 7, 14 and 30). Seven days after the final dose of Rabipur, the baby’s RVNA level was
2.34 IU/ml and, at the age of 2 years, the child was healthy and developing normally  [66].
Immunogenicity in malnourished children
Asia is home to over half of the world’s malnourished children. Approximately 50% of pre-
school age children suffer mild-to-moderate malnutrition, and over 90% of reported human
sc oo age c d e su e d to ode ate a ut t o , a d o e 90% o epo ted u a
rabies
 deaths occur
Full Article in Asia&
 Figures [63].Depending
data References on the type of
 Citations vaccine
Metrics administered, studies
 
examining the immune response to vaccination in children suffering from malnutrition have
reported varying results. Antibody responses to BCG for tuberculosis, and in some cases
polio vaccines, have been reported to be depressed in children with severe malnutrition,
whereas measles vaccine appears to be efficacious even in malnourished children  [67]. In
a study by Sampath and colleagues, 45 malnourished children aged 8 months to 16 years
who presented to the anti-rabies clinic in Hyderabad, India, for PEP were enrolled to be
investigated for their response to Rabipur. Thirty six children received five doses, three
received four doses and six received less than four doses of the vaccine. The 39 who
received four or more doses made it through to the per-protocol set  [63]. All bites were
evaluated as category II or III, in accordance with the WHO criteria  [8]. All children had
developed RVNA levels ≥0.5 IU/ml by Day 14. There was no significant difference in RVNA
concentrations between the malnutrition categories – immune response to Rabipur was
independent of the extent of malnutrition. In addition, there were no SAEs reported,
indicating that Rabipur is well tolerated in malnourished children (Table 3)  [63].
Immunogenicity in pregnancy
Rabies presents an intermediate risk to the unborn fetus of pregnant women  [68,69].
Whether the rabies virus can cross the placenta remains uncertain due to confounding
reports. A report from 1977 describes a pregnant woman infected with rabies who delivered
a premature baby before dying. Although the baby was not vaccinated, it did not develop
rabies. Other publications have also suggested that placental transmission of rabies virus in
humans is highly improbable  [68]. In 1981, however, a woman who was 9 months
pregnant presented to a hospital 34 days after being bitten by a rabid dog. Two days after
the mother was admitted to the hospital, the baby was born following induction of labor and
died suddenly 40.5 h later. The autopsy confirmed that both mother and baby had rabies.
This was the first reported case of human rabies acquired by placental transmission  [69].
The administration of Rabipur in pregnant women for PEP has been documented in a
retrospective case series on two pregnant women who had WHO category III exposure to a
suspected rabid animal at gestational Week 12. Each of the pregnant women got a total of
five doses of Rabipur: 1.0 ml IM on Days 0, 3, 7, 14 and 28 (Essen regimen) and equine rabies
immunoglobulin. Both vaccine and equine rabies immunoglobulin were well tolerated with
no reports of systemic or local AEs. The women had normal deliveries of healthy babies with
no evidence of congenital abnormalities  [70]. There is a clear consensus that pregnancy is

not a contraindication to rabies PEP  [71].
not a contraindication to rabies PEP  [71].
 
Immunogenicity in immunocompromised individuals
HIV-infected individuals generally have suboptimal immune responses to several commonly

used vaccines  [72,73]. Rabies vaccination differs from other immunizations in that it
represents prophylaxis of development of a fatal disease after virus exposure. However,
there has been a concern over whether the WHO-recommended PEP regimens provide
adequate RVNA levels in HIV-infected persons exposed to the rabies virus  [74]. Both IM
and ID rabies vaccination regimens have been reported to be less immunogenic in HIV-
infected patients  [71,74–78].
In HIV-infected individuals, administration of Rabipur (five-dose IM regimen; 1.0 ml single

doses on Days 0, 3, 7, 14 and 30) for PEP resulted in RVNA concentrations that were lower in
HIV-infected people than in uninfected controls (Table 4). While the response of RVNA was
7.75 IU/ml in the control group of healthy volunteers, levels were 1.09 IU/ml in asymptomatic
HIV patients and 0.31 IU/ml in symptomatic patients at Day 14. The percentage of patients
with RVNA ≥0.5 UI/ml was 100% in the control group, 64% in the asymptomatic group and
25% in the symptomatic HIV patients at Day 14  [79,80]. The development of antibody
levels in severely immunocompromised patients should therefore be checked 14 days after
the initiation of a rabies vaccination schedule  [45] and the guidance on the product label
should be followed  [56].
Immunogenicity of booster doses
The immunogenicity of Rabipur following a booster dose has been proven in PrEP in healthy
volunteers who have previously received Rabipur or HDCV (Table 5)  [34]. In addition, the
anamnestic response to booster doses of Rabipur has been demonstrated 14 years after the
last vaccination  [81]. Individuals were vaccinated with either IM or ID Rabipur according to
a three-dose PrEP schedule, followed by a 1.0 ml IM booster dose 2 years later. Subjects did
not receive any further booster doses. Fourteen years later, 10 individuals who provided
serum samples for analysis had adequate RVNA titers of >1:5, as defined by the Advisory
Committee on Immunization Practices, and received one 1.0 ml IM booster dose  [71].
Blood samples taken 24–45 days following the second booster demonstrated a high
anamnestic response of an approximate 10-fold increase in RVNA titers  [81]. Another
study demonstrated RVNA levels ≥0.5 IU/ml in individuals at least up to 6 years following
PrEP or PEP Rabipur regimens  [82].
Immunogenicity in nonclassical bat lyssavirus strains
Although the majority of human cases of rabies occur after exposure to classical rabies virus
 
transmitted by dog bite, bat-transmitted nonclassical rabies strains, such as European bat
lyssavirus type I (EBLV-I) and II and Australian bat lyssavirus, represent a source of human
rabies. The immunogenicity (cross-neutralizing activity) of Rabipur to these related lyssavirus
species was assessed in a laboratory study in which samples from healthy volunteers who
had received Rabipur in a simulated ID PEP regimen as part of a separate clinical trial were
analyzed. Rabipur induced adequate neutralizing antibodies to EBLV-1, EBLV-II and
Australian bat lyssavirus in 97, 100 and 100% of samples, respectively  [83].
Efficacy
Although there is no specific level of RVNA that is recognized as being ‘protective’ against
rabies in humans, the WHO recommends an RVNA concentration of ≥0.5 IU/ml as being
proof of an adequate immune response to vaccination  [8,44,45]. However, while
immunogenicity of a vaccine is a surrogate parameter, and no correlate of protection can be
established in humans for obvious ethical reasons, vaccine efficacy can be assessed by
investigating whether survival after an exposure has occurred. This is ideally done by looking
at survival after initiation of proper PEP following category II or III exposure to a laboratory-
confirmed rabid animal  [45]. Real survival data are available following administration of
Rabipur to rabies-exposed patients (Table 6). A prospective clinical trial assessing the efficacy
of a 0.1-ml dose of Rabipur administered ID was conducted in 113 patients presenting with
category III exposure from laboratory-confirmed rabid animals. Patients in the study were
vaccinated with 0.1 ml Rabipur via the Thai Red Cross regimen and monitored monthly for 1
year post exposure. The vaccine was well tolerated and no SAEs were reported. All patients
survived 1 year post exposure, confirming the efficacy of Rabipur  [53].
A summary of the efficacy data of Rabipur following PEP administration in response to

animal bites is listed in Table 6. These studies show that all patients who received Rabipur
following exposure to a rabid animal survived over the indicated observation period. This
demonstrated efficacy comes from robust data collected from several hundred patients of
different ages, including children, across many trials.
Rabipur post-marketing surveillance
The safety of PEP and PrEP with Rabipur has been assessed in a 10-year post-marketing
surveillance study in India in 1289 individuals including children from 1 year of age.
su e a ce study da 89 d dua s c ud g c de o yea o age.
Vaccination with Rabipur
 Full Article  Figureswas well tolerated,
& data Referenceswith only 4% ofsubjects
 Citations Metrics reporting AEs, all of

which were mild to moderate. The most commonly reported local adverse reactions in
subjects were injection-site pain (n = 26, 2.1%) and injection-site induration (n = 14, 1.1%).
Mild fever (37.2–37.8°C) occurred in six subjects (0.5%), which lasted 12–24 h following the
third or fourth vaccination  [64].
A 2007 safety review of RabAvert presented an analysis of post-licensure safety reports in

the USA from 1997 to 2005. The analysis, which used data collected via the Vaccine Adverse
Event Reporting System, showed that of approximately 1.1 million doses of vaccine
distributed in the USA during the study timeframe there were 336 AEs reported after
Rabipur administration – approximately 30 events per 100,000 doses. Twenty-four (7%) of
the AEs were considered serious by the reporters and there were no reports of death. The
authors concluded that the evaluation of Vaccine Adverse Event Reporting System reports
did not suggest a high frequency or unusual pattern of serious or other medically important
AEs, and most AEs were nonserious and consistent with pre-licensure safety data  [84].
Nearly 30 years of global usage of Rabipur confirms the well-balanced safety and tolerability
profile seen in clinical trials. The overall adverse drug reaction reporting rate for Rabipur in
the past 28.5 years is approximately 12.3 events per 100,000 doses sold. The vast majority
(nearly 80%) of reported events from Asia, Europe and the USA were nonserious reactions
known from clinical trials. The Medical Dictionary for Regulatory Activities, a clinically
validated international terminology dictionary, is organized by System Organ Class (SOC)
under which most of the reported Rabipur adverse drug reactions are classified.
Characteristics of SOC include general disorders and administration site conditions (24%),
nervous system disorders (18%) or musculoskeletal and connective tissue disorders (10%).
Within these SOCs, the most often reported symptoms were systemic reactions, such as
headache, dizziness, influenza-like illness and associated symptoms (e.g., fever, asthenia and
myalgia), and local injection-site-related reactions (e.g., redness, swelling and pain). Reports
on serious adverse drug reactions were in line with what is described in the current Rabipur
Core Safety Information or were reactions for which a causal relationship to Rabipur has not
been established. The general safety profile of Rabipur is as expected for an inactivated
vaccine and remains consistent with that shown in clinical trials.
Rabies PEP failure
There are reported incidences of people exposed to rabies virus developing clinical rabies
despite the administration of PEP. However, investigation into these cases shows that for the
desp te t e ad st at o o . o e e , est gat o to t ese cases s o s t at o t e
majority
 Fullof patients
Article there was
 Figures an omission
& data of atleast
 References one ofthe
Citations essential steps of PEP
Metrics  
(wound treatment, administration of RIG and complete course of vaccine)  [85–89].

Physicians should be advised that immediate and correct PEP management without delay
according to official recommendations is essential for patient survival.
However, there are very rare reported cases in which clinical rabies has developed in
immunologically healthy people despite apparently correct PEP regimen, including wound
treatment and timely administration of RIG and vaccine. A systematic review reported a total
of eight probable true vaccine failure cases in which Rabipur was administered in one case,
Rabipur and PVRV were given in a second case and an unknown vaccine in a third case
 [89]. More recently, a case of atypical initial clinical rabies symptoms that led to delayed
diagnosis was reported. The patient died despite appropriate PEP and administration of
Rabipur  [90].
Expert commentary
This review covers clinical trials that have contributed in a relevant and significant way to the
clinical development of Rabipur and to the definition of appropriate rabies vaccination
regimens. The development of rabies vaccines has come a long way, and cell-culture rabies
vaccines, such as Rabipur, have the benefit of inducing less severe adverse reactions
compared to formerly used NTVs. Not only does Rabipur induce an immune response after
IM administration, but it is also capable of stimulating a comparable immune response via
an ID route. Moreover, ID administration has significantly contributed to the affordability of
rabies vaccines in endemic, developing countries where it is endorsed by national health
authorities. Due to replacement of NTVs with cell-culture vaccines such as Rabipur, several
countries in Asia have come up with novel ID administration techniques to compensate for
logistical and economic challenges. With this shift to cell-culture vaccines, the management
of rabies represents a significant unmet global need, particularly in endemic, developing
countries. Despite the availability of effective vaccines, the number of human deaths from
rabies is unacceptably high  [91]. Human rabies vaccination is a critical component of the
PrEP and PEP regimens that should be followed before potential or after actual exposure to
the rabies virus. Three decades of widespread clinical use of Rabipur confirms its
immunogenicity and tolerability for both pre- and post-exposure vaccination regimens
among diverse populations. Wider use of human rabies vaccination for PrEP and PEP in
conjunction with programs to eradicate rabies from animal populations would be the right
direction in reducing the burden of disease. The most vulnerable populations to benefit from
d ect o educ g t e bu de o d sease. e ost u e ab e popu at o s to be e t o
such collaborated efforts
Full Article  Figuresare children,
& data particularly
 References in developing
 Citations countries. Technology exists
 Metrics  
to protect against rabies. If rabies is left unmanaged, it is virtually 100% fatal.

Five-year view
For over three decades, global and local health organizations and institutions have engaged
in the prevention and control of rabies, particularly in low- and middle-income countries. The
value of rabies vaccination remains unchanged, especially considering that several countries
aim to become rabies-free from 2020 to 2025. Widespread use of ID administration and
shorter ID PEP regimens could become a more common practice in other countries in Asia
and elsewhere. To support countries in their efforts to eliminate rabies, there is a need to
continue with and strengthen measurements such as enhancing awareness, rabies
education, teaching general prevention measures and providing appropriate rabies
immunization based on recommended vaccination regimens. The pathways to rabies
vaccine development have produced successful prophylaxis prevention and treatment used
to save individuals exposed to rabies. Furthermore, NTVs may be phased out in the next 5
years in the remaining few countries that still use this vaccine. PrEP and PEP regimens will be
further improved to maximize uptake and reduce clinical symptoms, for example, reduced
number of doses for IM PEP and condensed PEP ID regimens to 1 week. An abbreviated PrEP
regimen schedule for Rabipur may become officially available.
Acknowledgements
The authors wish to thank all of the many individuals who have participated in the clinical
development of Rabipur over the past 30 years.
Financial & competing interests disclosure
The authors are employees of Novartis Vaccines. The authors have no other relevant
affiliations or financial involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in the manuscript. P
Cates, of Apothecom, provided writing assistance that was paid for by Novartis Vaccines. K
Jenks, N Tong, of Novartis Vaccines, provided editorial support. D Gniel was an employee of
Je s, o g, o o a t s acc es, p o ded ed to a suppo t. G e as a e p oyee o
Novartis
 FullVaccines and
Article  Diagnostics
Figures atReferences
& data  the time ofparticipation
Citations and writing of this manuscript.
 Metrics  
Key issues
Rabies continues to cause high numbers of unnecessary human deaths in

endemic countries, despite available rabies biologicals for prevention and
treatment.
Children are at high risk for contracting rabies.
Rabipur is a cell-culture vaccine with long-lasting immunogenicity in different

populations including children.
Rabipur efficacy in preventing rabies after exposure to the virus has been
demonstrated in several clinical trials, and the vaccine showed a favorable
tolerability and safety profile.
30 years of clinical experience with Rabipur confirms the value of the vaccine in
human rabies prophylaxis.
References
1. Rabies (Fact sheet No. 99). World Health Organization. Available from:
www.who.int/mediacentre/factsheets/fs099/en/ [Last accessed 25 March 2014]
[Google Scholar]
2. Fekadu M, Endeshaw T, Alemu W, et al. Possible human-to-human transmission of rabies

in Ethiopia. Ethiop Med J 1996;34:123-7[PubMed], [Google Scholar]
3. Maier T, Schwarting A, Mauer D, et al. Management and outcomes after multiple corneal
and solid organ transplantations from a donor infected with rabies virus. Clin Infect Dis
2010;50:1112-19[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
4. Noah DL, Drenzek CL, Smith JS, et al. Epidemiology of human rabies in the United States,
1980 to 1996. Ann Intern Med 1998;128:922-30[Crossref], [PubMed], [Web of Science ®],
980 to 996. te ed 998; 8:9 30[C oss e ], [ ub ed], [ eb o Sc e ce ®],
[Google Scholar]

5. Smith J, Fishbein D, Rupprecht C, Clark K. Unexplained rabies in three immigrants in the
United States. A Virologic Investigation. N Engl J Med 1991;324(4):205-11 [Google Scholar]
6. Yousaf MZ, Qasim M, Zia S, et al. Rabies molecular virology, diagnosis, prevention and
treatment. Virol J 2012;9:50[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
7. Rabies. World Health Organization. Available from: www.who.int/rabies/en/ [Last accessed

25 March 2014] [Google Scholar]
8. WHO Expert Consultation on Rabies. Second report. World Health Organization. World
Health Organ Tech Rep Ser 2013(982):1-139; back cover [Google Scholar]
9. Bourhy H, Dautry-Varsat A, Hotez PJ, Salomon J. Rabies, still neglected after 125 years of
vaccination. PLoS Negl Trop Dis 2010;4:e839 [Google Scholar]
10. Sustaining the drive to overcome the global impact of neglected tropical diseases. Second
WHO report on neglected tropical diseases. World Health Organization; Geneva: 2013. p.
1-153 [Google Scholar]
11. Rupprecht CE, Shlim DR. Infectious diseases related to travel – rabies. In: Brunette G,
Kozarsky PE, Magill J, Shlim D, Whatley A, editors. CDC Health information for international
travel: The Yellow Book 2014. Oxford University Press; New York, NY: 2014. p. 270-6
[Google Scholar]
12. Kammer AR, Ertl HC. Rabies vaccines: from the past to the 21st century. Hybrid
Hybridomics 2002;21:123-7 [Google Scholar]
13. Javier RS, Kunishita T, Koike F, Tabira T. Semple rabies vaccine: presence of myelin basic
protein and proteolipid protein and its activity in experimental allergic encephalomyelitis. J
Neurol Sci 1989;93:221-30 [Google Scholar]
14. World Health Organization expert committee on rabies. Seventh report. World Health
Organ Tech Rep Ser 1984;709:1-104 [Google Scholar]
O ga ec ep Se 98 ; 09: 0 [Goog e Sc o a ]
 
15. Information Sheet: observed rate of vaccine reactions. Rabies Vaccine. World Health
Organization. Available from:
www.who.int/vaccine_safety/initiative/tools/Rabies_Vaccine_rates_information_sheet.pdf
[Last accessed 25 March 2014] [Google Scholar]
16. WHO Guide for Rabies Pre and Post Exposure Prophylaxis in Humans. World Health
Organization. Available from:
www.who.int/rabies/WHO_Guide_Rabies_Pre_Post_Exposure_Prophylaxis_Humans_2013.pdf
17. Fuenzalida E, Palacios R, Borgono JM. Antirabies antibody response in man to vaccine
made from infected suckling-mouse brains. Bull World Health Organ 1964;30:431-6
[PubMed], [Google Scholar]
18. Lavender JF, van Frank RM. Zonal-centrifuged purified duck embryo cell culture rabies
vaccine for human vaccination. Appl Microbiol 1971;22:358-65 [Google Scholar]
19. Fenje P. A rabies vaccine from hamster kidney tissue cultures: preparation and evaluation
in animals. Can J Microbiol 1960;6:605-9 [Google Scholar]
20. Kissling RE, Reese DR. Anti-Rabies vaccine of tissue culture origin. J Immunol 1963;91:362-
8 [Google Scholar]
21. Hicks DJ, Fooks AR, Johnson N. Developments in rabies vaccines. Clin Exp Immunol
22. Schwab MP, Fox JP, Conwell DP, Robinson TA. Avianized rabies virus vaccination in man.
Bull World Health Organ 1954;10:823-35 [Google Scholar]
23. Fox JP, Koprowski H, Conwell DP, et al. Study of antirabies immunization of man;
observations with HEP Flury and other vaccines, with and without hyperimmune serum, in
primary and recall immunizations. Bull World Health Organ 1957;17:869-904
[Google Scholar]
24. Plotkin SA. Vaccine production in human diploid cell strains. Am J Epidemiol 1971;94:303-6
[Google Scholar]
[Goog e Sc o a ]
 
25. Wiktor TJ, Koprowski H. Successful immunization of primates with rabies vaccine prepared
in human diploid cell strain WI-38. Proc Soc Exp Biol Med 1965;118:1069-73
[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
26. Turner GS, Aoki FY, Nicholson KG, et al. Human diploid cell strain rabies vaccine. Rapid
prophylactic immunisation of volunteers with small doses. Lancet 1976;1:1379-81
[Google Scholar]
27. Plotkin SA, Koprowski H. Rabies vaccines. In: Plotkin SA, Orenstein WA, Offit PA, editors.
Vaccines. Saunders Elsevier; Philadelphia: 2008. p. 687-714 [Google Scholar]
28. Garner WR, Jones DO, Pratt E. Problems associated with rabies preexposure prophylaxis.
JAMA 1976;235:131-2 [Google Scholar]
29. Barth R, Gruschkau H, Bijok U, et al. A new inactivated tissue culture rabies vaccine for use
in man. Evaluation of PCEC-vaccine by laboratory tests. J Biol Stand 1984;12:29-46
[Crossref], [PubMed], [Google Scholar]
30. Toovey S. Preventing rabies with the Verorab vaccine: 1985-2005 Twenty years of clinical
experience. Travel Med Infect Dis 2007;5:327-48 [Google Scholar]
31. Vodopija I, Ljubicic M, Baklaic Z. Antibody response to PCEC rabies vaccine following
abbreviated (3 dose) immunization schedules. In: Vodopija I, Nicholson KG, Smerdel S,
Bijok U, editors. Improvements in rabies post-exposure treatment. Zagreb Institute of
Public Health; Zagreb: 1985. p. 175-7 [Google Scholar]
32. Vodopija I, Sureau P, Lafon M, et al. An evaluation of second generation tissue culture
rabies vaccines for use in man: a four-vaccine comparative immunogenicity study using a
pre-exposure vaccination schedule and an abbreviated 2-1-1 postexposure schedule.
Vaccine 1986;4:245-8[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
33. Dreesen DW, Fishbein DB, Kemp DT, Brown J. Two-year comparative trial on the
immunogenicity and adverse effects of purified chick embryo cell rabies vaccine for pre-
exposure immunization. Vaccine 1989;7:397-400 [Google Scholar]

34. Briggs
 FullDJ, Dreesen
Article DW, Nicolay
 Figures & data U, et al. Purified
 References chick embryo
 Citations cell culture rabies vaccine:
 Metrics 
interchangeability with human diploid cell culture rabies vaccine and comparison of one
versus two-dose post-exposure booster regimen for previously immunized persons.
35. Rupprecht CE, Hanlon CA, Hemachudha T. Rabies re-examined. Lancet Infect Dis
36. Magpantay R, Bermal N, Medina P, Quiambao B. Safety and immunogenicity of rabies pre
and post exposure intradermal regimens using Abhayrab, a purified vero cell rabies
vaccine (PVRV) produced in India in healthy volunteers: towards greater affordability of
rabies prophylaxis. Asian Biomed 2010;4(1):61-7 [Google Scholar]
37. Sampath G, Madhusudana S, Sudarshan M, et al. Immunogenicity and safety study of

Indirab: a Vero cell based chromatographically purified human rabies vaccine. Vaccine
2010;28(24):4086-90 [Google Scholar]
38. Doddabele H, Shampur N, Gadey S, et al. Safety and immunogenicity study of a new
purified chick embryo cell rabies vaccine Vaxirab-N (Pitman-Moore strain) manufactured in
India. Human Vacc Immunother 2014;10(1):2796-801 [Google Scholar]
39. Barth R, Franke V. Purified chick-embryo cell vaccine for humans. In: Meslin FX, Kaplan
MM, Koprowski H, editors. Laboratory techniques in rabies. 4th edition. WHO; Geneva:
1996. p. 290-4 [Google Scholar]
40. WHO prequalified vaccines. World Health Organization. Available from:

www.who.int/immunization_standards/vaccine_quality/PQ_vaccine_list_en/en/index.html
41. Sampath G, Deshpande A, Briggs D, et al. Comparison of immunogenicity and safety of

Purified Chick Embryo Culture Rabies Vaccine (PCECV) manufactured in India with PCECV
manufactured in Germany. Proceedings of the XIII International Meeting on Research
Advances and Rabies Control in the Americas. 2002 [Google Scholar]
42. Zhu FC, Wu CH, Meng FY. [Safety and immunogenicity of rabies vaccine (chick embryo cell)
for human use produced in Germany and India (transl)]. Zhongguo Yi Miao He Mian Yi
o u a use p oduced Ge a ya d d a (t a s )]. o gguo ao e a
2009;15:447-50 [Google
 Full Article  Figures &Scholar]
data  References  Citations  Metrics  

43. Finke S, Karger A, Freuling C, Müller T. Assessment of inactivated human rabies vaccines:
biochemical characterization and genetic identification of virus strains. Vaccine
44. Briggs DJ; World Health Organization. The immunological basis for immunization series.
Module 17: Rabies. Available from:
http://whqlibdoc.who.int/publications/2011/9789241501088_eng.pdf [Last accessed 25
March 2014] [Google Scholar]
45. Rabies vaccines: world Health Organization position paper. Wkly Epidemiol Rec
2010;32:309-20 [Google Scholar]
46. Centers for Disease Control and Prevention. Use of a reduced (4-dose) vaccine schedule
for postexposure prophylaxis to prevent human rabies. Recommendations of the Advisory
Committee on Immunization Practices. MMWR Recomm Rep 2010;59(RR-2):1-9
[Google Scholar]
47. World Health Organization expert committee on rabies. Eighth report. World Health Organ
Tech Rep Ser 1992;824:1-84 [Google Scholar]
48. Scheiermann N, Baer J, Hilfenhaus J, et al. Reactogenicity and immunogenicity of the newly
developed purified chick embryo cell (PCEC)-rabies vaccine in man. Zentralbl Bakteriol
Mikrobiol Hyg A 1987;265:439-50[PubMed], [Google Scholar]
49. Liu H, Huang G, Tang Q, et al. The immunogenicity and safety of vaccination with purified
Vero cell rabies vaccine (PVRV) in China under a 2-1-1 regimen. Hum Vaccin 2011;7:220-4
[Taylor & Francis Online], [Web of Science ®], [Google Scholar]
50. Vodopija I, Sureau P, Smerdel S, et al. Interaction of rabies vaccine with human rabies
immunoglobulin and reliability of a 2-1-1 schedule application for postexposure
treatment. Vaccine 1988;6:283-6[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
51. Beran J, Honegr K, Banzhoff A, Malerczyk C. Potency requirements of rabies vaccines

administered intradermally using the Thai Red Cross regimen: investigation of the
ad ste ed t ade a y us g t e a ed C oss eg e : est gat o o t e
immunogenicity
 Full Article of serially
Figures diluted
& data purified chick
 References embryo cell
 Citations rabies vaccine. Vaccine
 Metrics  

52. Briggs DJ, Banzhoff A, Nicolay U, et al. Antibody response of patients after postexposure
rabies vaccination with small intradermal doses of purified chick embryo cell vaccine or
purified Vero cell rabies vaccine. Bull World Health Organ 2000;78:693-8
[PubMed], [Web of Science ®], [Google Scholar]
53. Quiambao BP, Dimaano EM, Ambas C, et al. Reducing the cost of post-exposure rabies
prophylaxis: efficacy of 0.1 ml PCEC rabies vaccine administered intradermally using the
Thai Red Cross post-exposure regimen in patients severely exposed to laboratory-
confirmed rabid animals. Vaccine 2005;23:1709-14
54. Suntharasamai P, Chaiprasithikul P, Wasi C, et al. A simplified and economical intradermal

regimen of purified chick embryo cell rabies vaccine for postexposure prophylaxis. Vaccine
55. Wasi C, Chaiprasithikul P, Auewarakul P, et al. The abbreviated 2-1-1 schedule of purified
chick embryo cell rabies vaccination for rabies postexposure treatment. Southeast Asian J
Trop Med Public Health 1993;24:461-6[PubMed], [Google Scholar]
56. Novartis Vaccines. Rabipur summary of product characteristics. 2010 [Google Scholar]
57. Lumbiganon P, Chaiprasithikul P, Sookpranee T, et al. Pre-exposure vaccination with

purified chick embryo cell rabies vaccines in children. Asian Pac J Allergy Immunol
1989;7:99-101[PubMed], [Web of Science ®], [Google Scholar]
58. Shanbag P, Shah N, Kulkarni M, et al. Protecting Indian schoolchildren against rabies: pre-
exposure vaccination with purified chick embryo cell vaccine (PCECV) or purified verocell
rabies vaccine (PVRV). Hum Vaccin 2008;4:365-9
[Taylor & Francis Online], [Web of Science ®], [Google Scholar]
59. Pengsaa K, Limkittikul K, Sabchareon A, et al. A three-year clinical study on

immunogenicity, safety, and booster response of purified chick embryo cell rabies vaccine
u oge c ty, sa ety, a d booste espo se o pu ed c c e b yo ce ab es acc e
administered
 Full Article intramuscularly
 Figures & data orintradermally to 12- to 18-month-old
References  Citations  Metrics Thai children,  
concomitantly with Japanese encephalitis vaccine. Pediatr Infect Dis J 2009;28:335-7

60. Kamoltham T, Thinyounyong W, Phongchamnaphai P, et al. Pre-exposure rabies

vaccination using purified chick embryo cell rabies vaccine intradermally is immunogenic
and safe. J Pediatr 2007;151:173-7[Crossref], [PubMed], [Web of Science ®],
[Google Scholar]
61. Kamoltham T, Thinyounyong W, Khawplod P, et al. Immunogenicity of simulated PCECV

postexposure booster doses 1, 3, and 5 Years after 2-dose and 3-dose primary rabies
vaccination in schoolchildren. Adv Prev Med 2011;2011:403201[Crossref], [PubMed],
[Google Scholar]
62. Ogutu BR, Apollo OJ, McKinney D, et al. Blood stage malaria vaccine eliciting high antigen-
specific antibody concentrations confers no protection to young children in Western
Kenya. PLoS One 2009;4:e4708[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
63. Sampath G, Parikh S, Sangram P, Briggs DJ. Rabies post-exposure prophylaxis in

malnourished children exposed to suspect rabid animals. Vaccine 2005;23:1102-5
64. Sehgal S, Bhattacharya D, Bhardwaj M. Ten year longitudinal study of efficacy and safety of
purified chick embryo cell vaccine for pre- and post-exposure prophylaxis of rabies in
Indian population. J Commun Dis 1995;27:36-43[PubMed], [Google Scholar]
65. Sehgal S, Bhardwaj M, Bhattacharya D. Immunogenicity and feasibility of purified chick

embryo cell vaccine. Indian Pediatr 1994;31:133-7[PubMed], [Google Scholar]
66. Lumbiganon P and Wasi C. Survival after rabies immunisation in newborn infant of
affected mother. Lancet 1990;336:319 [Google Scholar]
67. Adeiga AA, Akinosho RO, Onyewuche J. Evaluation of immune response in infants with
different nutritional status: vaccinated against tuberculosis, measles and poliomyelitis. J
Trop Pediatr 1994;40:345-50[Crossref], [PubMed], [Web of Science ®], [Google Scholar]

68. Müller-Holve
 Full Article W,Leitritz H,data
Figures & KnorrE. [Early development
References  Citations of
a Metrics
child following rabies of the

mother during pregnancy (author’s transl)]. Infection 1977;5:49-50 [Google Scholar]

69. Sipahioglu U, Alpaut S. [Transplacental rabies in humans (transl)]. Mikrobiyol Bul

1985;19:95-9 [Google Scholar]
70. Sudarshan MK, Giri MS, Mahendra BJ, et al. Assessing the safety of post-exposure rabies
immunization in pregnancy. Hum Vaccin 2007;3:87-9[Taylor & Francis Online],
[Google Scholar]
71. Manning SE, Rupprecht CE, Fishbein D, et al. Human Rabies Prevention – United States
2008. Recommendations of the Advisory Committee on Immunization Practices. MMWR
Recomm Rep 2008;57(RR-3):1-28[PubMed], [Google Scholar]
72. Barbi M, Bardare M, Luraschi C, et al. Antibody response to inactivated polio vaccine (E-
IPV) in children born to HIV positive mothers. Eur J Epidemiol 1992;8:211-16
[Google Scholar]
73. Kroon FP, van Dissel JT, de Jong JC, van Furth R. Antibody response to influenza, tetanus
and pneumococcal vaccines in HIV-seropositive individuals in relation to the number of
CD4+ lymphocytes. AIDS 1994;8:469-76[Crossref], [PubMed], [Web of Science ®],
[Google Scholar]
74. Jaijaroensup W, Tantawichien T, Khawplod P, et al. Postexposure rabies vaccination in

patients infected with human immunodeficiency virus. Clin Infect Dis 1999;28:913-14
[Google Scholar]
75. Tantawichien T, Jaijaroensup W, Khawplod P, Sitprija V. Failure of multiple-site intradermal

postexposure rabies vaccination in patients with human immunodeficiency virus with low
CD4+ T lymphocyte counts. Clin Infect Dis 2001;33(10):e122-4 [Google Scholar]
76. Thisyakorn T, Pancharoen C, Wilde H. Immunologic and virologic evaluation of HIV-

infected children after rabies vaccination. Vaccine 2001;19(2001):1534-7 [Google Scholar]
77. Gelinck L, Jol-van der Zijde C, Jansen-Hoogendijk A, et al. Restoration of the antibody
response upon rabies vaccination in HIV-infected patients treated with HAART. AIDS
espo se upo ab es acc at o ected pat e ts t eated t . S
2009;23:2451-8 [Google
 Full Article  Figures &Scholar]
data  References  Citations  Metrics  

78. Pancharoen C, Thisyakorn U, Tantawichien T, et al. Failure of pre- and postexposure rabies
vaccinations in a child infected with HIV. Scand J Infect Dis 2001;33:390-1
79. Deshpande A, Briggs DJ, Banzhoff A. Investigation of immune response To purified chick
embryo cell tissue culture rabies vaccine (PCECV) in HIV infected individuals using a
simulated post-exposure regimen. Proceedings of the XIII International AIDS Conference;
2000. 163-8 [Google Scholar]
80. Deshpande A, Briggs DJ. Rabies vaccination in immunosuppressed patients. In: Dodet B,
Meslin FX, Heseltine E, editors. Rabies Control in Asia. Fourth International Symposium on
Rabies Control in Asia John Libbey Eurotext; Montrouge: 2001. p. 58-60 [Google Scholar]
81. Malerczyk C, Briggs DJ, Dreesen DW, Banzhoff A. Duration of immunity: an anamnestic
response 14 years after rabies vaccination with purified chick embryo cell rabies vaccine. J
Travel Med 2007;14:63-4[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
82. Thraenhart O, Kreuzfelder E, Hillebrandt M, et al. Long-term humoral and cellular

immunity after vaccination with cell culture rabies vaccines in man. Clin Immunol
Immunopathol 1994;71:287-92[Crossref], [PubMed], [Google Scholar]
83. Malerczyk C, Selhorst T, Tordo N, et al. Antibodies induced by vaccination with purified
chick embryo cell culture vaccine (PCECV) cross-neutralize non-classical bat lyssavirus
strains. Vaccine 2009;27:5320-5[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
84. Dobardzic A, Izurieta H, Woo EJ, et al. Safety review of the purified chick embryo cell rabies
vaccine: data from the Vaccine Adverse Event Reporting System (VAERS), 1997-2005.
85. Deshmukh DG, Damle AS, Bajaj JK, et al. Fatal rabies despite post-exposure prophylaxis.
Indian J Med Microbiol 2011;29:178-80[Crossref], [PubMed], [Web of Science ®],
[Google Scholar]
86. Fescharek R, Schwarz S, Quast U, et al. Postexposure rabies prophylaxis: when the
guidelines are not respected. Vaccine 1991;9:868-72 [Google Scholar]
gu de es a e ot espected. acc e 99 ;9:868 [Goog e Sc o a ]
 
87. Madhusudana SN, Aggarwal P, Tripathi KK. Failure of rabies postexposure treatment with
purified chick embryo cell (PCEC) vaccine. Vaccine 1989;7:478-9 [Google Scholar]
88. Wilde H, Sirikawin S, Sabcharoen A, et al. Failure of postexposure treatment of rabies in

children. Clin Infect Dis 1996;22:228-32[Crossref], [PubMed], [Web of Science ®],
[Google Scholar]
89. Wilde H. Failures of post-exposure rabies prophylaxis. Vaccine 2007;25:7605-9

90. Shantavasinkul P, Tantawichien T, Wacharapluesadee S, et al. Failure of rabies

postexposure prophylaxis in patients presenting with unusual manifestations. Clin Infect
Dis 2010;50:77-9 [Google Scholar]
91. Wunner WH, Briggs DJ. Rabies in the 21 century. PLoS Negl Trop Dis 2010;4:e591
[Google Scholar]
92. Bijok U, Barth R, Gruschkau H, et al. Clinical trials in healthy volunteers with the new
purified chick embryo cell rabies vaccine for man. J Commun Dis 1984;16:61-9[PubMed],
[Google Scholar]
93. Bijok U, Vodopija I, Smerdel S. Purified chick embryo cell (PCEC) rabies vaccine for human
use: clinical trials. Behring Inst Mitt 1984;76:155-64 [Google Scholar]
94. Bijok U. Purified chick embryo cell (PCEC) rabies vaccine – A review of the clinical
development 1982-1984. In: Vodopija I, Nicholson KG, Smerdel S, Bijok U, editors.
Improvements in Rabies Post-Exposure Treatment. Zagreb Institute of Public Health;
Zagreb: 1985. p. 103-11 [Google Scholar]
95. Barth R, Bijok U, Gruschkau H, et al. Purified chicken embryo cell rabies vaccine for human
use. Lancet 1983;1:700 [Google Scholar]
96. Wasi C, Chaiprasithikul P, Chavanich L, et al. Effective pre- and post-exposure treatment
with purified chick embryo rabies vaccine. J Infect Dis Antimicrob Agents 1985;2:67-73
t pu ed c c e b yo ab es acc e. J ect s t c ob ge ts 985; :6 3
[Google Scholar]

97. Wasi C, Chaiprasithikul P, Chavanich L, et al. Purified chick embryo cell rabies vaccine.
Lancet 1986;1:40[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
98. Nicholson KG, Farrow PR, Bijok U, Barth R. Pre-exposure studies with purified chick
embryo cell culture rabies vaccine and human diploid cell vaccine: serological and clinical
responses in man. Vaccine 1987;5:208-10 [Google Scholar]
99. Suntharasamai P, Warrell MJ, Viravan C, et al. Purified chick embryo cell rabies vaccine:
economical multisite intradermal regimen for post-exposure prophylaxis. Epidemiol Infect
100. Madhusudana SN, Tripathi KK. Post exposure studies with human diploid cell rabies
vaccine and purified chick embryo cell vaccine: comparative serological responses in man.
Zentralbl Bakteriol 1989;271:345-50[Crossref], [PubMed], [Google Scholar]
101. Natarajan M, Mukundan P, John TJ. Immune response to purified chick embryo cell culture
rabies vaccine manufactured in India. Indian J Med Res 1992;95:51-3
[PubMed], [Web of Science ®], [Google Scholar]
102. Kulkarni R, Thatte U, Shinde V, et al. A comparison of the tolerability of two dilution
volumes (0.5 mL and 1.0 mL) of a purified chick embryo cell rabies vaccine administered
intramuscularly to healthy adult volunteers: a randomized, intraindividual, assessor-blind
study. Curr Ther Res 2004;65:47-56 [Google Scholar]
103. Tanterdtham S, Chaiprasithikul P, Yuthavong K, Wasi C. Follow-up of protective antibody

level after post-exposure vaccination with purified tissue culture rabies vaccine (PCEC)
small doses intradermally. J Med Assoc Thai 1991;74:498-501[PubMed], [Google Scholar]
104. Meesomboon V, Kingnate D, Samuthananont P. Antibody response to PCEC rabies vaccine

following 0.1 ml immunization regimens. Com Dis J 1992;18:108-13 [Google Scholar]
105. Charanasri U, Meesomboon V, Kingnate D, et al. Intradermal simulated rabies

postexposure prophylaxis using purified chick embryo rabies vaccine. J Med Assoc Thai
poste posu e p op y a s us g pu ed c c e b yo ab es acc e. J ed ssoc a
1992;75:639-43[PubMed], [Google Scholar]

106. Madhusudana SN, Anand NP, Shamsundar R. Economical multi-site intradermal regimen
with purified chick embryo cell vaccine (Rabipur) prevents rabies in people bitten by
confirmed rabid animals. Int J Infect Dis 2002;6:210-14[Crossref], [PubMed],
[Google Scholar]
107. Madhusudana SN, Sanjay TV, Mahendra BJ, Suja MS. Simulated post-exposure rabies
vaccination with purified chick embryo cell vaccine using a modified Thai Red Cross
regimen. Int J Infect Dis 2004;8:175-9[Crossref], [PubMed], [Web of Science ®],
[Google Scholar]
108. Chhabra M, Ichhpujani RL, Bhardwaj M, et al. Safety and immunogenicity of the
intradermal Thai red cross (2-2-2-0-1-1) post exposure vaccination regimen in the Indian
population using purified chick embryo cell rabies vaccine. Indian J Med Microbiol
2005;23:24-8[Crossref], [PubMed], [Google Scholar]
109. Sudarshan MK, Madhusudana SN, Mahendra BJ, et al. Evaluation of a new five-injection,
two-site, intradermal schedule for purified chick embryo cell rabies vaccine: a randomized,
open-label, active-controlled trial in healthy adult volunteers in India. Curr Ther Res
2005;66:323-34[Crossref], [PubMed], [Google Scholar]
110. Ambrozaitis A, Laiskonis A, Balciuniene L, et al. Rabies post-exposure prophylaxis

vaccination with purified chick embryo cell vaccine (PCECV) and purified Vero cell rabies
vaccine (PVRV) in a four-site intradermal schedule (4-0-2-0-1-1): an immunogenic, cost-
effective and practical regimen. Vaccine 2006;24:4116-21
111. Madhusudana SN, Sanjay TV, Mahendra BJ, et al. Comparison of saftey and
immunogenicity of purified chick embryo cell rabies vaccine (PCECV) and purified vero cell
rabies vaccine (PVRV) using the Thai Red Cross intradermal regimen at a dose of 0.1 ML.
Hum Vaccin 2006;2:200-4[Taylor & Francis Online], [Web of Science ®], [Google Scholar]
112. Sudarshan MK, Narayana DH, Madhusudana SN, et al. Evaluation of a one week
intradermal regimen for rabies post-exposure prophylaxis: results of a randomized, open
t ade a eg e o ab es post e posu e p op y a s: esu ts o a a do ed, ope
label, active-controlled
 Full Article  Figurestrial in healthy
& data adult volunteers
 References  Citations in 
India. Hum Vaccin Immunother
Metrics  
2012;8:1077-81[Taylor & Francis Online], [Web of Science ®], [Google Scholar]

113. Sirikwin S, Likanonsakul S, Waradejwinyoo S, et al. Antibody response to an eight-site

intradermal rabies vaccination in patients infected with Human Immunodeficiency Virus.
114. Vodopija R, Lafont M, Baklaic Z, et al. Persistence of humoral immunity to rabies 1100 days
after immunization and effect of a single booster dose of rabies vaccine. Vaccine
115. Ljubicic M, Vodopija I, Smerdel S, et al. Efficacy of PCEC vaccine in post-exposure rabies
prophylaxis. In: Vodopija I, Nicholson KG, Smerdel S, Bijok U, editors. Improvements in
rabies post-exposure treatment. Zagreb Institute of Public Health; Zagreb: 1985. p. 95-101
[Google Scholar]
116. Tanphaichitra D, Siristonpun Y. Study of the efficacy of a purified chick embryo cell vaccine
in patients bitten by rabid animals. Int Med 1987;3:158-60 [Google Scholar]
117. Sehgal S, Bhardwaj M, Bhatia R. Clinical evaluation of purified chick embryo cell antirabies
vaccine for post-exposure treatment. J Commun Dis 1988;20:293-300[PubMed],
[Google Scholar]
118. Vodopija I, Smerdel S, Bijok U. PCEC rabies vaccine and HRIG in post-exposure protection
against rabies. In: Kuwert EK, Mérieux C, Koprowski H, Bögel K, editors. Rabies in the
Tropics. Springer; Berlin Heidelberg: 1985. p. 133-7 [Google Scholar]
119. Kamoltham T, Singha J, Promsaranee U, et al. Elimination of human rabies in a canine

endemic province in Thailand: five-year programme. Bull World Health Organ
2003;81:375-81[PubMed], [Web of Science ®], [Google Scholar]


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30 Years of Rabies Vaccination With Rabipur - A Summary of Clinical Data and Global Experience - Expert Review of Vaccines - Vol 14, No 3

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10/15/2018 30 years of rabies vaccination with Rabipur: a summary of clinical data and global experience: Expert Review of Vaccines:

f Vaccines: Vol 14, …

Expert Review of Vaccines 

30 years of rabies vaccination with Rabipur:

 Download citation  https://doi.org/10.1586/14760584.2015.1011134

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reported to be provided to children  [1,11].

Rabies vaccines – historical development

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Category I is insigniﬁcant or no exposure to the animal and therefore requires no

Category III is transdermal bite or scratches or contamination of mucous membrane or

Rabipur clinical trials

Table 6. Summary of Rabipur efficacy following PEP

Table 1. Summary of Rabipur intramuscular PEP and PrEP

Table 2. Summary of Rabipur intradermal PEP and PrEP

Table 3 Rabipur PEP and PrEP immunogenicity and safety

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Table 4. Rabipur immunogenicity in HIV-infected individuals.

CSV Display Table

Immunogenicity in PEP & PrEP regimens

A pivotal immunogenicity study assessed several vaccination regimens in 88 healthy

The immunogenicity of Rabipur when administered using the WHO-recommended Zagreb

Immunogenicity following ID administration

authorities  [8]. ID administration is a more economic and antigen-saving alternative to IM

Immunogenicity in malnourished children

no evidence of congenital abnormalities  [70]. There is a clear consensus that pregnancy is

HIV-infected individuals generally have suboptimal immune responses to several commonly

In HIV-infected individuals, administration of Rabipur (ﬁve-dose IM regimen; 1.0 ml single

Immunogenicity of booster doses

Immunogenicity in nonclassical bat lyssavirus strains

A summary of the eﬃcacy data of Rabipur following PEP administration in response to

Rabipur post-marketing surveillance

A 2007 safety review of RabAvert presented an analysis of post-licensure safety reports in

Rabies PEP failure

(wound treatment, administration of RIG and complete course of vaccine)  [85–89].

to protect against rabies. If rabies is left unmanaged, it is virtually 100% fatal.

Financial & competing interests disclosure

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Rabies continues to cause high numbers of unnecessary human deaths in

Children are at high risk for contracting rabies.

Rabipur is a cell-culture vaccine with long-lasting immunogenicity in different

2. Fekadu M, Endeshaw T, Alemu W, et al. Possible human-to-human transmission of rabies

 Reprints & Permissions  PDF

7. Rabies. World Health Organization. Available from: www.who.int/rabies/en/ [Last accessed

exposure immunization. Vaccine 1989;7:397-400 [Google Scholar]

37. Sampath G, Madhusudana S, Sudarshan M, et al. Immunogenicity and safety study of

40. WHO prequaliﬁed vaccines. World Health Organization. Available from:

41. Sampath G, Deshpande A, Briggs D, et al. Comparison of immunogenicity and safety of

 Reprints & Permissions  PDF

51. Beran J, Honegr K, Banzhoff A, Malerczyk C. Potency requirements of rabies vaccines

2005;23:3902-7[Crossref], [PubMed], [Web of Science ®], [Google Scholar]

54. Suntharasamai P, Chaiprasithikul P, Wasi C, et al. A simpliﬁed and economical intradermal

56. Novartis Vaccines. Rabipur summary of product characteristics. 2010 [Google Scholar]

57. Lumbiganon P, Chaiprasithikul P, Sookpranee T, et al. Pre-exposure vaccination with

59. Pengsaa K, Limkittikul K, Sabchareon A, et al. A three-year clinical study on

concomitantly with Japanese encephalitis vaccine. Pediatr Infect Dis J 2009;28:335-7

60. Kamoltham T, Thinyounyong W, Phongchamnaphai P, et al. Pre-exposure rabies

61. Kamoltham T, Thinyounyong W, Khawplod P, et al. Immunogenicity of simulated PCECV

63. Sampath G, Parikh S, Sangram P, Briggs DJ. Rabies post-exposure prophylaxis in

65. Sehgal S, Bhardwaj M, Bhattacharya D. Immunogenicity and feasibility of puriﬁed chick

Trop Pediatr 1994;40:345-50[Crossref], [PubMed], [Web of Science ®], [Google Scholar]

mother during pregnancy (author’s transl)]. Infection 1977;5:49-50 [Google Scholar]

69. Sipahioglu U, Alpaut S. [Transplacental rabies in humans (transl)]. Mikrobiyol Bul