Sabin
live attenuated Oral Poliovirus Vaccine (OPV)
In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was
licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent oral
poliovirus vaccine (OPV) was licensed and largely replaced IPV use. OPV
is manufactured by Lederle Laboratories Division, American Cynamid Company
(Pearle River, NY). Trivalent OPV contains
live attenuated strains of all three serotypes of poliovirus in a 10:1:3
ratio. The viruses were attenuated by serial passage in monkey kidney,
Vero, or human diploid fibroblast cell cultures, allowing it to accumulate
mutations. Ultimately, this resulted in an attenuated virus that could
be given to a patient orally. The weaker virus replicates normally in the
intestine, but cannot grow well enough to invade the central nervous system.
The vaccine is supplied as a single 0.5 ml dose in a plastic dispenser.
The vaccine contains trace amounts of streptomycin and neomycin. The vaccine
potency is stabilized with molar magnesium chloride or sucrose. OPV replicates
in the ororpharyngeal and gastrointestinal tract and in lymph nodes that
drain the intestine. OPV induces two separate immune responses. First,
OPV activates the humoral immune response, prompting the production of
serum-neutralizing antibodies in the blood to all three polio serotypes.
This systemic response is long lasting and helps to prevent the spread
of poliovirus to the nervous system. OPV also produces a mucosal immune
response consisting of interferon and virus-specific IgA antibody in the
epithelial lining of the ororpharyngeal and gastrointestinal tract. Only
primates are susceptible to all three serotypes of poliovirus, so the safety
of oral poliovirus vaccine (OPV) and its consistency have been tested in
the monkey neurovirulence test (MNVT). About 100 monkeys are used for each
trivalent vaccine batch. In a number of countries, the MNVT is performed
twice, once by the manufacturer and once by the national control authority.
In addition to the high cost, monkeys are usually obtained from the wild
with a potential for transmitting exotic diseases to humans. An alternative
animal system being evaluated is susceptible transgenic mice expressing
the human poliovirus receptor.
Advantages
OPV is given orally rather than by injection. Its administration does
not require a trained health worker and sterile injection equipment. At
a current price of 8 US cents a dose, the vaccine is relatively inexpensive,
facilitating mass purchasing of the vaccine during National Immunization
Days. Short-term shedding of OPV in the stools of recently immunized persons
can result in the passive immunization of persons within close contact.
OPV is highly effective in producing immunity to poliovirus. A single dose
of OPV produces immunity to all three vaccine viruses in about 50% of recipients.
Three doses produces immunity to all 3 poliovirus types in more than 95%
of recipients. Immunity from oral poliovirus vaccine is probably life long.
OPVís ability to stimulate mucosal immunity is responsible for the success
of OPV mass campaigns in interrupting wild poliovirus transmission. Therefore,
OPV remains the vaccine of choice for the eradication of polio. OPV intestinal
immunity reduces the chance that a vaccinated person will become infected
with wild virus if he or she is exposed while visiting a polio endemic
country.
Disadvantages
The greatest concern with the use of live attenuated vaccines is their
potential for reversion to neurovirulence. All three OPV vaccine strains
show some tendency to revert to neurovirulence. Sabin types 2 and 3 vaccine
viruses revert more easily to neurovirulence phenotypes as compared to
type 1. However, none of the serotypes are genetically unstable. Single-base
mutations that are strongly associated with attenuation and reversion to
neurovirulence have been identified. Major attenuating mutations for all
three serotypes have been identified in the 5p non-coding region (NCR),
at position 480 for type 1, 481 for type 2, and 472 for type 3. For type
3, an additional point mutation associated with both attenuation and temperature
sensitivity has been identified at position 2034 in theVP3 capsid gene.
The three serotypes of OPV are relatively unstable during passage in cell
culture and have been found to be unstable and rapidly lost during replication
in the human gastrointestinal tract. Vaccination with OPV results in the
release of a variety of live mutant viruses in the feces. Despite the excellent
safety record of OPV, in approximately 1 in every 3 million doses of the
vaccine, the live attenuated vaccine virus in OPV can cause paralysis in
the vaccinated child or in a close contact. This extremely low risk of
vaccine-associated polio (VAPP) is accepted by most public health programs
in the world because hundreds of thousands of children would be crippled
every year without OPV. Another pathogen may be acting in synchrony with
polio to suppress the immune system enough to allow the mutant viruses
to enter the nervous system. Temperature instability of a live virus vaccine
is also a major factor. However, OPV is able to be stabilized within a
solution of magnesium chloride. OPV in MgCl2 is stable for at
least twelve months at 4C, six weeks at 25C, and sufficiently immunogenic
to use after one week at 37C.
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Advantages
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Disadvantages
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Sabin Vaccine (OPV)
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a. Relatively inexpensive and easily administrated
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a. Can mutate to more virulent strain
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b. Induces both systemic and local immunity
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b. Less reliable in tropical areas (see MgCl2
discussion)
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c. Prepared in human cells eliminating risk of latnet
viruses found in monkey
kidney cells |
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d. Induces herd immunity
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