Vaccine (IPV)
By: Paul Brogee, Julia Manalil, Vikshit Girish Patel, Leila
Emami Taba, and Arpit Dharambhai Thumar
February 10, 2016
ChE 660
M. Aucoin
Poliovirus
1,2,3
Family:
Genus: Enterovirus
Picornaviridae
Genome:
+
single-stranded
RNA
Capsid: Composed of 60 heterotetramers
(VP1-4), arranged in icosahedral symmetry,
approximately 30 nm in diameter.
Envelope: None
Serotypes:
3
(PV1,
Entry: Via CD155 receptor
Transmission:
Reservoir:
PV2,
PV3)
Fecal-Oral
Humans
Poliomyelitis
Poliovirus typically infects the pharynx and GItract, resulting in asymptomatic or minor illness
(e.g., sore throat, fever)
Aseptic meningitis and paralytic poliomyelitis
occur when poliovirus spreads to motor
neurons and the central nervous system (CNS).
Cases are then divided into spinal, bulbar, and
spinobulbar classes based on localization of
infection.
Paralytic poliomyelitis results in death in 15-30%
of adult cases, and 2-5% in juveniles. Death is
caused by asphyxiation due to paralysis of the
respiratory system.
Figure
2:
Distribution
of
resultant
presentations due to poliovirus infection in
humans.
Epidemiology
4,5,6
Country
Wild-type
Cases
cVDPV
Cases
Afghanista
n
19
Guinea
Lao
Madagasca
r
10
Myanmar
Nigeria
Pakistan
53
Ukraine
There are two forms of the polio vaccine: Inactivated Polio Vaccine (IPV) developed by Jonas Salk in
1952 and Oral Polio Vaccine (OPV) developed by Albert Sabin
Inactivated Polio Vaccine
Administered orally.
In Canada, there are two manufacturers of IPV, Sanofi Pasteur and GlaxoSmithKline.
Trivalent IPV is a clear, colourless liquid vaccine. It is distributed in single doses as prefilled sterile
syringes, or in sterile vials for 5 and 10 dose presentations.
Each 0.5ml dose contains the following components:
3 serotypes of inactivated poliovirus:
Type 1 (Mahoney) - 40 D-antigen units
Type 2 (MEF1) - 8 D-antigen units
Type 3 (Saukett) - 32 D-antigen units
M-199 media
2-phenoxyethanol (0.5%)
Trace amounts of:
Formalin (<0.02%)
Neomycin (<5ng)
Streptomycin (<200ng)
Polymyxin B (<25ng)
Residual calf bovine serum (<50ng)
MRC-5
Vero
Source
Human
male lung
fibroblast
cells
African green
monkey
kidney
epithelial
cells
Media
CMRL 1969
medium w/
bovine calf
serum
EMEM
medium w/
bovine calf
serum
Sanofi
Td Polio
Imovax Polio
8,12,13
12,13,14
Step 3: Clarification
12,14,15
Once the resulting viral suspension has been harvested, the slurry is thinned, and excess
cellular debris is removed.
1. Harvested viral suspensions are filtered through a 75 m stainless steel sieve to remove
any microcarriers, followed by 0.45 and 0.22 m combination filtration. Sieves are pretreated with Celite, to improve filter performance.
2. Filtration units operate at set point for both inlet and outlet pressure, as well as retentate
cross flow rate, temperature, concentration and filter load.
3. Following each batch, units are flushed with 3-4 mL of fresh M199 medium to maintain
filter efficacy.
Step 4: Concentration
12,14,15,16
Step 5: Purification
12,13,14,15
Step 6: Inactivation
8,12,14,17
Figure 6: Formaldehyde
1. After purification and inactivation, monovalent suspensions from each of the three
poliovirus serotypes are mixed to produce a trivalent solution. The mixture is a 5:1:4 ratio
of PV1, PV2, and PV3, respectively.
2. The final trivalent mixture is homogenized and filtered using a 0.22 m cellulose ester
membrane.
3. After passing quality assurance, it is diluted and filled in vials for a final concentration of
(per 0.5 ml dose):
a. Type 1 (Mahoney) - 40 D-antigen units
b. Type 2 (MEF1) - 8 D-antigen units
c. Type 3 (Saukett) - 32 D-antigen units
Vaccines are classified for packaging on the basis of their thermostability and presentation.
IPV is designated as Class A Packing which requires temperatures to not exceed +8 C.
Temperature monitoring devices are included in all vaccine shipments to document whether
temperature limits have been exceeded.
The storage volume of the vaccine varies according to the type of vaccine, the number of
doses per vial, and the dimensions of the vial and secondary packaging.
Labeling is done for Primary Packaging (first level of container for the vaccine), Secondary
packaging (intermediate packaging that contains the primary packages) and Tertiary
packaging (the shipping container that contains the secondary packages)
Standard shipping and arrival procedures depend on the country of destination.
Approaches to Achieve an
Affordable IPV 13
One proof of concept study aimed to make IPV production more affordable by using the OPV Sabin strains but
processing them similar to IPV (sIPV). This was in an effort to reduce the biosafety risk of manufacturing wild polio,
ultimately lowering the cost of manufacturing and allowing it to be a process that can be conducted in middle- to lowincome countries. Below is a summary of the recovery of virus at each step in the manufacturing process. Low yields
for Sabin type 2 were observed, bringing into question whether this would be a competitive method compared to the
current methods. Nevertheless, studies are continuing down this avenue and products worthy of clinical trials are
being tested.
Approaches to Achieve an
Affordable IPV 19
Reduce Number of IPV Doses - Studies show new evidence that if 1 or 2 doses are sufficiently
immunogenic, the number of doses in an IPV schedule could be reduced. Research is being conducted
on whether a single dose of IPV can prime the immune system against poliovirus.
Intradermal Administration - Intradermal injection provides improved immune response as
compared to intramuscular injection, and thus requires a smaller quantity of vaccine. It may also be
administered by a non-medically trained person.
Adjuvants- IPV production cost can be reduced by the use of adjuvant to enhance immunogenicity. A
number of research groups have evaluated traditional adjuvants such as aluminium,
oligodeoxynucleotides and Vitamin D3 as being useful in reducing the magnitude of required
antigens.
Optimization of Production Processes The development of IPV from safer poliovirus strains and
noninfectious methods of production have become a priority. In addition, producers in developing
countries can take advantage of specific optimization techniques for current IPV production and can
further reduce costs.
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