Poliovirus Vaccine, Inactivated

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 doses8 of IPV vaccine than the vaccine available in the United States prior to 1988.

Studies in developed8 and developing9,10 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

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

REFERENCES

1. van Wezel AL, et al. Inactivated poliovirus vaccine: Current production methods and new developments. Rev Infect Dis 6 (Suppl 2): S335-S340, 1984.

2. Montagnon BJ, et al. Industrial scale production of inactivated poliovirus vaccine prepared by culture of Vero cells on microcarrier. Rev Infect Dis 6 (Suppl 2): S341-S344, 1984.

3. McBean AM, et al. Serologic response to oral polio vaccine and enhanced-potency inactivated polio vaccines. Am J Epidemiol 128: 615-628, 1988.

4. Murdin AD, et al. Inactivated poliovirus vaccine: past and present experience. Vaccine 8: 735-746, 1996.

5. Sabin AB. Poliomyelitis. In Brande AI, Davis CE, Fierer J (eds) International Textbook of Medicine, Vol II. Infectious Diseases and Medical Microbiology. 2nd ed. Philadelphia, WB Saunders, 1986.

6. Prevots DR, et al. Vaccine-associated paralytic poliomyelitis in the United States, l980- 1994: current risk and potential impact of a proposed sequential schedule of IPV followed by OPV (Abstract #H90). In: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC. American Society for Microbiology, 179, 1996.

7. ACIP. Updated Recommendations of the Advisory Committee on Immunization Practices. Poliomyelitis Prevention in the United States. MMWR 49: No. RR-5, 2000.

8. Salk J, et al. Antigen content of inactivated poliovirus vaccine for use in a one- or two-dose regimen. Ann Clin Res 14: 204-212, 1982.

9. Salk J, et al. Killed poliovirus antigen titration in humans. Develop Biol Standard 41: 119­132, 1978.

10. Salk J, et al. Theoretical and practical considerations in the application of killed poliovirus vaccine for the control of paralytic poliomyelitis. Develop Biol Standard 47: 181-198, 1981.

11. Unpublished data available from Sanofi Pasteur SA.

12. Unpublished data available from Sanofi Pasteur Inc.

13. Faden H, et al. Comparative evaluation of immunization with live attenuated and enhanced potency inactivated trivalent poliovirus vaccines in childhood: Systemic and local immune responses. J Infect Dis 162: 1291-1297, 1990.

14. Vidor E, et al. The place of DTP/eIPV vaccine in routine pediatric vaccination. Rev Med Virol 4: 261-277, 1994.

15. Bottiger M. Long-term immunity following vaccination with killed poliovirus vaccine in Sweden, a country with no circulating poliovirus. Rev Infect Dis 6 (Suppl 2): S548-S551, 1984.

16. Plotkin SA, et al. Inactivated polio vaccine for the United States: a missed vaccination opportunity. Pediatr Infect Dis J 14: 835-839, 1995.

17. Marine WM, et al. Limitation of fecal and pharyngeal poliovirus excretion in Salk- vaccinated children. A family study during a Type 1 poliomyelitis epidemic. Amer J Hyg 76: 173-195, 1962.

18. Bottiger M, et al. Vaccination with attenuated Type 1 poliovirus, the Chat strain. II. Transmission of virus in relation to age. Acta Paed Scand 55: 416-421, 1966.

19. Dick GWA, et al. Vaccination against poliomyelitis with live virus vaccines. Effect of previous Salk vaccination on virus excretion. Brit Med J 2: 266-269, 1961.

20. Wehrle PF, et al. Transmission of poliovirus; III. Prevalence of polioviruses in pharyngeal secretions of infected household contacts of patients with clinical disease. Pediatrics 27: 762-764, 1961.

21. Adenyi-Jones SC, et al. Systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine in premature and term infants. J Pediatr 120: No 5, 686-689, 1992.

22. Chin TDY. Immunity induced by inactivated poliovirus vaccine and excretion of virus. Rev Infect Dis 6 (Suppl 2): S369-S370, 1984.

23. Salk D. Herd effect and virus eradication with use of killed poliovirus vaccine. Develop Biol Standard 47: 247-255, 1981.

24. Bijerk H. Surveillance and control of poliomyelitis in the Netherlands. Rev Infect Dis 6 (Suppl 2): S451-S456, 1984.

25. Lapinleimu K. Elimination of poliomyelitis in Finland. Rev Infect Dis 6 (Suppl 2): S457- S460, 1984.

26. Conyn van Spaendonck M, et al. Circulation of Poliovirus during the poliomyelitis outbreak in the Netherlands in 1992-1993. Amer J Epidemiology 143: 929-935, 1996.

27. Strebel PM, et al. Epidemiology of poliomyelitis in the United States one decade after the last reported case of indigenous wild virus associated disease. Clin Infect Dis 14: 568-579, 1992.

• It is used to prevent polio.

• Tell all of your health care providers that you take poliovirus vaccine. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may not protect all people who use it. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use poliovirus vaccine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin or a muscle.
• Your doctor will give this medicine.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

For all patients taking poliovirus vaccine:

• Redness or swelling where the shot is given.
• Pain where the shot was given.
• Irritation where the shot is given.

Young children:

• Feeling fussy.
• Feeling tired or weak.
• Not hungry.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

• Enhanced-Potency Inactivated Poliovirus Vaccine
• IPV
• Salk Vaccine

Poliovirus prevention:

Active immunization of infants (≥6 weeks [US labeling]; ≥2 months [Canadian labeling]), children, adolescents, and adults for prevention of poliomyelitis caused by poliovirus types 1, 2, and 3.

US labeling: Infants (as young as 6 weeks), children, adolescents, and adults

Canadian labeling: Infants (as young as 2 months), children, adolescents, and adults

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for the following:

• All infants and children (first dose given at 2 months of age) (CDC/ACIP, 58[30] 2009)

Routine immunization of adults in the United States is generally not recommended. Adults with previous wild poliovirus disease, who have never been immunized, or those who are incompletely immunized may receive inactivated poliovirus vaccine if they fall into one of the following categories (CDC/ACIP [Prevots 2000]):

• Travelers to regions or countries where poliomyelitis is endemic or epidemic

• Healthcare workers in close contact with patients who may be excreting poliovirus

• Laboratory workers handling specimens that may contain poliovirus

• Members of communities or specific population groups with diseases caused by wild poliovirus

• Incompletely vaccinated or unvaccinated adults in a household or with other close contact with children receiving oral poliovirus (may be at increased risk of vaccine associated paralytic poliomyelitis)

Belimumab: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Patients should receive inactivated vaccines prior to initiation of belimumab therapy whenever possible, due to the risk for an impaired response to the vaccine during belimumab therapy. Consider therapy modification

Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Consider therapy modification

Immunosuppressants: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Exceptions: Cytarabine (Liposomal). Consider therapy modification

Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy

Animal reproduction studies have not been conducted. Although adverse effects of IPV have not been documented in pregnant women or their fetuses, vaccination of pregnant women should be avoided on theoretical grounds. Pregnant women at increased risk for infection and requiring immediate protection against polio may be administered the vaccine (CDC/ACIP [Prevots 2000]).