Vaccine Information: IPOL

IPOL- poliovirus type 1 antigen (formaldehyde inactivated), poliovirus type 2 antigen (formaldehyde inactivated) and poliovirus type 3 antigen (formaldehyde inactivated) injection, suspension
Sanofi Pasteur Inc.

AHFS Category: 80:12 IPV

Rx only

DESCRIPTION

IPOL® , Poliovirus Vaccine Inactivated, produced by Sanofi Pasteur SA, is a sterile suspension of three types of poliovirus: Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett). IPOL vaccine is a highly purified, inactivated poliovirus vaccine with enhanced potency. Each of the three strains of poliovirus is individually grown in vero cells, a continuous line of monkey kidney cells cultivated on microcarriers. (1) (2) The cells are grown in Eagle MEM modified medium, supplemented with newborn calf bovine serum tested for adventitious agents prior to use, originated from countries free of bovine spongiform encephalopathy. For viral growth, the culture medium is replaced by M-199, without calf bovine serum. This culture technique and improvements in purification, concentration, and standardization of poliovirus antigen produce a more potent and consistent immunogenic vaccine than the inactivated poliovirus vaccine (IPV) available in the US prior to 1988. (3) (4)

After clarification and filtration, viral suspensions are concentrated by ultrafiltration, and purified by three liquid chromatography steps; one column of anion exchanger, one column of gel filtration, and again one column of anion exchanger. After re-equilibration of the purified viral suspension with Medium M-199 and adjustment of the antigen titer, the monovalent viral suspensions are inactivated at +37°C for at least 12 days with 1:4000 formalin.

Each dose (0.5 mL) of trivalent vaccine is formulated to contain 40 D antigen units of Type 1, 8 D antigen units of Type 2, and 32 D antigen units of Type 3 poliovirus. For each lot of IPOL vaccine, D-antigen content is determined in vitro using the D-antigen ELISA assay. IPOL vaccine is produced from vaccine concentrates diluted with M-199 medium. Also present are 0.5% of 2-phenoxyethanol and a maximum of 0.02% of formaldehyde per dose as preservatives. Neomycin, streptomycin, and polymyxin B are used in vaccine production; and, although purification procedures eliminate measurable amounts, less than 5 ng neomycin, 200 ng streptomycin, and 25 ng polymyxin B per dose may still be present. The residual calf bovine serum albumin is less than 50 ng/dose in the final vaccine.

The vaccine is clear and colorless and should be administered intramuscularly or subcutaneously.

The vial stopper is not made with natural rubber latex.

CLINICAL PHARMACOLOGY

Poliomyelitis is caused by poliovirus Types 1, 2, or 3. It is primarily spread by the fecal-oral route of transmission but may also be spread by the pharyngeal route.

Approximately 90% to 95% of poliovirus infections are asymptomatic. Nonspecific illness with low-grade fever and sore throat (minor illness) occurs in 4% to 8% of infections. Aseptic meningitis occurs in 1% to 5% of patients a few days after the minor illness has resolved. Rapid onset of asymmetric acute flaccid paralysis occurs in 0.1% to 2% of infections, and residual paralytic disease involving motor neurons (paralytic poliomyelitis) occurs in approximately 1 per 1,000 infections. (5)

Prior to the introduction of inactivated poliovirus vaccines in 1955, large outbreaks of poliomyelitis occurred each year in the United States (US). The annual incidence of paralytic disease of 11.4 cases/100,000 population declined to 0.5 cases by the time oral poliovirus vaccine (OPV) was introduced in 1961. Incidence continued to decline thereafter to a rate of 0.002 to 0.005 cases per 100,000 population. Of the 127 cases of paralytic poliomyelitis reported in the US between 1980 and 1994, six were imported cases (caused by wild polioviruses), two were “indeterminate” cases, and 119 were vaccine associated paralytic poliomyelitis (VAPP) cases associated with the use of live, attenuated oral poliovirus vaccine (OPV). (6) An all IPV schedule was adopted in 1999 to eliminate VAPP cases. (7)

Poliovirus Vaccine Inactivated induces the production of neutralizing antibodies against each type of virus which are related to protective efficacy. Antibody response in most children was induced after receiving fewer doses (8) of IPV vaccine than the vaccine available in the United States prior to 1988.

Studies in developed (8) and developing (9), (10) countries with a similar enhanced IPV manufactured by the same process as IPOL vaccine in primary monkey kidney cells have shown a direct relationship exists between the antigenic content of the vaccine, the frequency of seroconversion, and resulting antibody titer. Approval in the US was based upon demonstration of immunogenicity and safety in US children. (11)

In the US, 219 infants received three doses of a similar enhanced IPV at two, four, and eighteen months of age manufactured by the same process as IPOL vaccine except the cell substrate for IPV was using primary monkey kidney cells. Seroconversion to all three types of poliovirus was demonstrated in 99% of these infants after two doses of vaccine given at 2 and 4 months of age. Following the third dose of vaccine at 18 months of age, neutralizing antibodies were present at a level of ≥1:10 in 99.1% of children to Type 1 and 100% of children to Types 2 and 3 polioviruses. (3)

IPOL vaccine was administered to more than 700 infants between 2 to 18 months of age during three clinical studies conducted in the US using IPV only schedules and sequential IPV-OPV schedules. (12) (13) Seroprevalence rates for detectable serum neutralizing antibody (DA) at a ≥1:4 dilution were 95% to 100% (Type 1); 97% to 100% (Type 2) and 96% to 100% (Type 3) after two doses of IPOL vaccine depending on studies.

Table 1: US Studies with IPOL Vaccine Administered Using IPV Only or Sequential IPV-OPV Schedules
Age (months) for Post Dose 2 Post Dose 3 Pre Booster Post Booster
2 4 6 12 to 18 Type 1 Type 2 Type 3 Type 1 Type 2 Type 3 Type 1 Type 2 Type 3 Type 1 Type 2 Type 3
Dose 1 Dose 2 Dose 3 Booster N * %DA %DA %DA N * %DA %DA %DA N * %DA %DA %DA N * %DA %DA %DA
I IPOL vaccine given either separately in association with DTP in two sites (s) or combined (c) with DTP in a dual chambered syringe
O OPV
*
N = Number of children from whom serum was available
Detectable antibody (neutralizing titer ≥1:4)
IPOL vaccine given subcutaneously
§
NA – No poliovirus vaccine administered
IPOL vaccine given intramuscularly
STUDY 1 (11)
I(s) I(s) NA § I(s) 56 97 100 97 53 91 97 93 53 97 100 100
O O NA O 22 100 100 100 22 78 91 78 20 100 100 100
I(s) O NA O 17 95 100 95 17 95 100 95 17 100 100 100
I(s) I(s) NA O 17 100 100 100 16 100 100 94 16 100 100 100
STUDY 2 (10)
I(c) I(c) NA I(s) 94 98 97 96 100 92 95 88 97 100 100 100
I(s) I(s) NA I(s) 68 99 100 99 72 100 100 94 75 100 100 100
I(c) I(c) NA O 75 95 99 96 77 86 97 82 78 100 100 97
I(s) I(s) NA O 101 99 99 95 103 99 97 89 107 100 100 100
STUDY 3 (10)
I(c) I(c) I(c) O 91 98 99 100 91 100 100 100 41 100 100 100 40 100 100 100
I(c) I(c) O O 96 100 98 99 94 100 100 99 47 100 100 100 45 100 100 100
I(c) I(c) I(c) + O O 91 96 97 100 85 100 100 100 47 100 100 100 46 100 100 100

In one study, (13) the persistence of DA in infants receiving two doses of IPOL vaccine at 2 and 4 months of age was 91% to 100% (Type 1), 97% to 100% (Type 2), and 93% to 94% (Type 3) at twelve months of age. In another study, (12) 86% to 100% (Type 1), 95% to 100% (Type 2), and 82% to 94% (Type 3) of infants still had DA at 18 months of age.

In trials and field studies conducted outside the US, IPOL vaccine, or a combination vaccine containing IPOL vaccine and DTP, was administered to more than 3,000 infants between 2 to 18 months of age using IPV only schedules and immunogenicity data are available from 1,485 infants. After two doses of vaccine given during the first year of life, seroprevalence rates for detectable serum neutralizing antibody (neutralizing titer ≥1:4) were 88% to 100% (Type 1); 84% to 100% (Type 2) and 94% to 100% (Type 3) of infants, depending on studies. When three doses were given during the first year of life, post-dose 3 DA ranged between 93% to 100% (Type 1); 89% to 100% (Type 2) and 97% to 100% (Type 3) and reached 100% for Types 1, 2, and 3 after the fourth dose given during the second year of life (12 to 18 months of age). (14)

In infants immunized with three doses of an unlicensed combination vaccine containing IPOL vaccine and DTP given during the first year of life, and a fourth dose given during the second year of life, the persistence of detectable neutralizing antibodies was 96%, 96%, and 97% against poliovirus Types 1, 2, and 3, respectively, at six years of age. DA reached 100% for all types after a booster dose of IPOL vaccine combined with DTP vaccine. (11) A survey of Swedish children and young adults given a Swedish IPV only schedule demonstrated persistence of detectable serum neutralizing antibody for at least 10 years to all three types of poliovirus. (15)

IPV is able to induce secretory antibody (IgA) produced in the pharynx and gut and reduces pharyngeal excretion of poliovirus Type 1 from 75% in children with neutralizing antibodies at levels less than 1:8 to 25% in children with neutralizing antibodies at levels more than 1:64. (4) (14) (16) (17) (18) (19) (20) (21) (22) There is also evidence of induction of herd immunity with IPV, (15) (23) (24) (25) (26) and that this herd immunity is sufficiently maintained in a population vaccinated only with IPV. (26)

VAPP has not been reported in association with administration of IPOL vaccine. (27) It is expected that an IPV only schedule will eliminate the risk of VAPP in both recipients and contacts compared to a schedule that included OPV. (7)

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