Formulation, Efficacy and Immunogenicity Studies of a Liquid State Rabies
Vaccine with Magnesium Chloride as Stabilizer
Selvaraj J
1*
, Rajendran V
2*
, Kuruba B
3
, Channappa SK
1
, Pachamuthu RG
4
and Raju MK
1
1
Pasteur Institute of India, Coonoor, Tamilnadu, India
2
Department of Biochemistry, North Eastern Hill University, Shillong, Meghalaya, India
3
Cell and Molecular Biology Lab, Illinois Institute of Technology, Chicago
4
Department of Biotechnology, Jamal Mohammed College, Trichirapalli, Tamilnadu, India
*
Corresponding author: Selvaraj J, Pasteur Institute of India, Coonoor, Pin-643103, Tamilnadu, India, Tel: +919894967811; +919089540954; E-mail:
vijayakumar.thenilgiris@gmail.com, seljag2005@yahoo.com
Received date: Jul 04, 2015; Accepted date: Aug 24, 2015; Published date: Aug 28, 2015
Copyright: © 2015 Selvaraj J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Propagation of fixed rabies virus strain in vero cell line, ultra filtration of rabies viral harvest, betapropiolactone
inactivation subsequent purification, total protein nitrogen quantification, Rapid Fluorescent focus inhibition test,
MgCl
2
based liquid rabies vaccine formulation (TCALRV-B) and immune response analysis. The vero cell derived
PV 11 rabies viral titers were found that 10
-5.3
, ultra filtrated, betapropiolactone inactivated and viral protein qualities
were within the range (WHO). The total protein concentration and PN
2
was 577.6, 0.26 mg/ml respectively. The host
cellular protein and residual cellular DNA was 16 ng/single human doses and below 100 pg/ml respectively it reveals
within the limit. The RFFIT titer of the TCALRV-B possessed higher immune response (8 IU/ml) of rabies
neutralizing antibodies on 14
th
on 21
st
day the titer was four fold increasing even after 90
th
day it reveals its
immunopotency. The TCALRV-B contained all the quality attributes to fulfill the regulatories although it contained
potency, immunogenicity and safety as in vivo study shows lesser immunogenic during the booster doses. This may
be due to the unadsorption of rabies viral proteins by MgCl
2
as adjuvant.
Key words:
Rabies vaccine; Tissue culture; Human albumin; Magnesium
chloride; RFFIT; SRID
Introduction
Rabies is one of the neglected tropical diseases caused by the
lyssavirus, causing severe encephalomyelitis throughout the world. It
thought to be one of the oldest diseases of mankind. In Asia, rabies is
one of the most important diseases because high human mortality rate
and high costs spend for prevention and treatment, A survey has
shown that Asia carries a larger part of the public health burden of
with an estimated 32,000 deaths [1], and 20,000 of human deaths in
India every year [2]. India has approximately 25 million dogs, with a
dog: man ratio was 1:36. 1.1 to 1.5 million persons gets post-exposure
rabies vaccine annually in India and hence the annual requirement for
rabies vaccine is approximately 6-10 million doses. The post exposure
prophylaxis of rabies disease requires 4-5 doses of highly expensive cell
culture derived vaccines for the entire period of immunization, in
which case the poor people are unable to bear the cost. The high cost
of cell culture rabies vaccine is due to the increased cost of production.
Most of the available cell culture vaccines are in freeze dried form
whereas processing of the rabies vaccine the maximum cost is needed
for downstream purification and lyophilization process [3].
The currently available cell culture rabies viral vaccines were
formulated with human albumin and maltose as a freeze dried state,
various stabilizers are added during the preparation, in case of freeze
dried vaccines it is mandatory, the immunogen presence was weak
amount. If sufficient amounts of various preservative materials were
not added while lyophilization, the vaccine would not be readily
observable and undoubtedly adhere to the wall of the vaccine vial. But
during the freeze drying process there is a losses of considerable
antigenicity (immunogenic and potency) in the presence of human
serum albumin the binding strength of rabies viral protein [4].
The Lyophilization process is a multistage operation in which, each
step is utmost importance and critical, this process has to be adapted
to individual vaccines according to the specific requirements, low-
temperature behavior of the different products. The formulated and
filled vaccine materials are hardened while freezing process due to low
temperatures, during this period; all fluids present become solid
bodies, either crystalline, amorphous, or glass. Keeping this view in
this study to do the liquid formulation of vero cell derived rabies
vaccine with MgCl
2
as a stabilizer as well as adjuvant.
Materials and Methods
Vero cell propagation of rabies virus
Vero cells (CCL-81) were obtained from the American Type
Culture Collection (ATCC) at the passage number 125 as monolayer’s
frozen cells and propagated with appropriate medium [5]. Further it
was revived, sub cultured and seeded into roller bottles (2.5 × 10
-6
cells/ml) [6] and the cultures were incubated at 37°C at 0.6 rpm. Fixed
strain of Pasteur virus (PV-11) which was obtained from Institute
Pasteur France was propagated and infected with vero cell line and the
virus infectivity was analyzed [5,6]. The rabies infected vero cell
supernatant (viral harvest) was collected and replenished with
maintenance medium at every intervals of 72 hrs for 4 harvests, it was
Vaccines & Vaccination
Selvaraj et al., J Vaccines Vaccin 2015, 6:4
http://dx.doi.org/10.4172/2157-7560.1000292
Research Article Open Access
J Vaccines Vaccin
ISSN:2157-7560 JVV, an open access journal
Volume 6 • Issue 4 • 1000292