Status: approvals withdrawn; no longer manufactured

Organizations involved:

Lederle Labs. – Manuf.; R&D; Tech.; Former

Wyeth – World mark.; Parent; Former

World Health Organization (WHO) – Tech.; Former

Cross ref.: See the Polio Vaccine Products entry (#516). See also the entries below for each of the separately approved poliovirus strain components of this vaccine.

Description: Poliovirus Vaccine Live Oral Trivalent or Orimune is an aqueous formulation of three types (strains) of live attenuated poliovirus, Sabin types 1, 2 and 3, obtained from independent culture in African green monkey kidney cells. The medium used for virus propagation is Eagle’s basal medium consisting of Earle’s balanced salt solution containing amino acids, antibiotics, and calf serum (with older labeling also reporting lact-al-bumin hydrolysate). After cell growth, the medium is replaced with fresh medium containing no calf serum. The final vaccine is diluted with a modified cell culture maintenance medium containing sorbitol, and the final product is essentially the live viruses dissolved in maintenance medium. Each 0.5 mL dose of Orimune contains less than 25 µg each of the antibiotics, streptomycin and neomycin (residual from culture media).

Potency of the oral poliovirus vaccine is expressed in terms of the median tissue culture infective dose (TCID50). The vaccine contains viral titers of 105.4 to 106.5 (5.4-6.4 log) of type 1 virus, 104.5 to 105.5 (4.5-5.5 log) of type 2 virus, and 105.2 to 106.2 (5.2-6.2 log) of type 3 virus using the monkey kidney tube titration method (see CFR 630.17). Infectivity is 106.0 to 107.7 (6.0-7.0 log) for type 1 virus, 105.1 to 106.1 (5.1-6.1 log) for type 2 virus, and 105.8 to 106.8 (6.0-7.0 log) for type 3 virus using the more sensitive Hep-2 microtitration method (see J. Biol. Stand., vol. 1, p. 91-97, 1983). To maintain potency, the vaccine must be stored below 0˚C (32˚F; frozen). The sorbitol in the virus medium maintains it as a fluid and prevents freezing down to -14˚C (7˚F). The vaccine contains phenol red dye as a pH indicator, and typically appears pink.

The vaccine was packaged in disposable, single-dose, 0.5 mL plastic pipettes. For administration, the plastic cap was removed and the contents expelled into the mouth.

Nomenclature: Poliovirus Vaccine, OPV [BIO]; Orimune [TR]; Poliovirus Vaccine Live Oral Trivalent [FDA]; Poliovirus Vaccine Live Oral Trivalent (Sabin Strains Types 1, 2 and 3) [FDA]; Poliovirus Vaccine Live Oral [USAN]; Poliovirus Vaccine Live Oral USP [USP]; Sabin vaccine [SY]; OPV [SY]; NDC 0005-2084-08; NDC 0005-2084-12 [NDC]

Biological.: This live oral poliovirus vaccine normally induces asymptomatic infection in the gastrointestinal tract that simulates natural infection. This low-level infection induces both mucosal (IgA) and humoral (IgG) poliovirus antibodies capable of opsonization, neutralization, and complement activation. The viruses persists in the gastrointestinal tract for 4-6 weeks, during which live virus is shed in feces.

History: See the Polio Vaccine Products entry (#516) for further information about polio vaccine development.

The World Health Organization (WHO) and other non-commercial organizations, e.g., Wistar Institute and Pasteur Institute, played important roles in the development and introduction of oral poliovirus vaccine (OPV). WHO handled (and continues to manage) distribution of the vaccine in a number of countries. Much of the major international polio vaccination efforts using OPV vaccines occurred in parallel with the introduction and adoption of inactivated polio vaccines (IPV). WHO initiated studies that set standards and permitted the large scale trials of Sabin OPV and other live attenuated vaccines. Large-scale OPV trials were conducted in the U.S.S.R. and other countries, and OPV vaccines were adopted for worldwide usage. Surveillance by WHO Collaborative Centers established the safety of OPV vaccines and first identified issues of reversion (mutation to pathogenicity) for the vaccine strains (primarily type 3 viruses).

See the History section of the Polio Vaccine Products entry (#516) for discussion that OPV use in Africa contributed to or caused the HIV/AIDS pandemic.

In 2000, 45 cases of polio or suspected polio occurred on the island of Hispaniola (Dominican Republic and Haiti); the first report of a polio outbreak in the Americas in a decade. The outbreak was caused by a strain of poliovirus that originated in OPV. The normally harmless attenuated virus apparently acquired pathogenicity-conferring mutations during passage in this under-vaccinated population.

Companies.: Orimune was commercially developed and is manufactured by Lederle Labs./Wyeth (Pearl River, NY; formerly a subsidiary of American Cyanamid, then American Home Products Corp., now Wyeth), CBER/FDA est. no. 0017. Presumably, with Wyeth having largely left the vaccine market, except for Prevnar, this vaccine is no longer manufactured, even for use in other countries. The vaccine was marketed in the U.S. and internationally by Wyeth and affiliates.

FDA class: Biologic PLA

CBER class: Viral And Rickettsial Vaccines

Approvals: Date = 19630625; first approval, PLA; Indication = for routine immunization of infants and children at 2 and 4 months, 6 to 18 months, and 4 to 6 years of age

Date = 19851002; approval revoked and granted (reissued) with a new (current) proper name

Indications: [full text of the "INDICATIONS AND USAGE” section from recent product insert/labeling]:

For poliovirus prophylaxis:

Adults: 0.5 mL PO initially, then repeated 8 weeks later. The third dose should be given 8-12 months after the second dose. When less than 4 weeks is available before immunization is required, a single 0.5 mL PO dose should be given.

Infants: The first 0.5 mL PO dose should be administered at 6-12 weeks of age. The second 0.5 mL PO dose should be administered preferably 8 weeks after the first dose. The third 0.5 mL PO dose should be administered at 6 months of age, however, if this time cannot be met, the third dose may be administered as late as 18 months of age. Children up to age 18 years: 0.5 mL PO initially, followed by the second dose preferably 8 weeks after the first dose. The third dose is given 8-12 months after the second dose (adolescents and older children may receive the third dose 6-8 weeks after the second dose if there is an increased risk of poliomyelitis). Booster doses are suggested upon starting school at 4-6 years of age, unless the third dose of the primary series was given after the recipient’s fourth birthday.

Patients with renal impairment: Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Status: OPV is no longer used for routine vaccinations in the U.S. FDA approval was recently revoked (no longer appears on lists of approved products). The inactivated vaccine, IPOL, is now the preferred vaccine, except for certain special circumstances. See the Polio Vaccine Products entry (#516) for further information.

Tech. transfer: The World Health Organization (WHO) has reported that it has held an exclusive license to live oral poliovirus vaccine technology since 1972. The WHO has apparently simply has not required licensing (having placed the technology in the public domain for all to freely use), or has granted nonexclusive licenses to various organizations and companies worldwide at no or negligible cost. Any original OPV related manufacturing, formulation and use patents have long expired.

Medical: A causal relationship has been established between OPV and rare paralytic poliomyelitis in vaccinees and their close contacts. This is due to mutation of the virus back to wild-type virus virulence and pathogenicity. See the Polio Vaccine Products entry (#516). The attenuated viruses in Orimune (and other OPVs) can cause paralytic polio due to unchecked infection in immune compromised, e.g., AIDS, patients. Available studies indicate that Orimune dose not significantly increase the risk of Guillain-Barre Syndrome (GBS), transverse myelitis, mortality from Sudden Infant Death Syndrome (SIDS), or death from causes other than poliomyelitis.

The live polioviruses in Orimune after administration are shed in the vaccinee’s feces for up to 6-8 weeks and shed via the pharyngeal route for 1-2 weeks. During this time household and other persons coming into oral contact with shed virus may also become infected (and effectively vaccinated) with the vaccine strains.

The Centers for Disease Control and Prevention (CDC) reports that about 303 million doses of OPV were administered in the U.S. during 1980-1994. During this period, there were 133 confirmed cases of paralytic poliomyelitis of which nearly all, 125, were Orimune-associated (1 case per 2.4 million doses). Among the 125 cases, 49 occurred in vaccine recipients (1 case/6.2 million doses), 40 in contacts of vaccinees (1 case/7.6 million doses), 30 in immunodeficient recipients or contacts (1 case/10.1 million doses), and six in persons with no history of vaccine exposure (from whom vaccine-like strains were isolated). The CDC estimates a frequency of poliomyelitis paralysis for vaccine recipients of one case/1.4 million first doses and a lower frequency for subsequent doses. For contacts, the frequency of paralysis is one case/2.2 million first doses. Overall, the frequency of paralysis is 1 case/750,000 first doses and one case/5.1 million subsequent doses.

With wild-type poliovirus now nearly eradicated, Orimune is the main source for poliovirus infections in the U.S. and other countries using this vaccine. Orimune is being phased out in the U.S. (and other developed countries) in favor of IPV. See the Poliovirus Vaccine Products entry (#516) for further information about poliovirus eradication efforts and the abandonment of live vaccines in favor of inactivated vaccines.

Market: Since its introduction, over 650 million doses of Orimune had been distributed in the U.S. Between 1961-1978, Orimune had 70%-80% of the U.S. OPV market, and 100% after 1978 (as the only manufacturer). The World Health Organization (WHO), United Nations, has estimated that over 2 billion doses of oral polio vaccines are still manufactured annually worldwide. See the Polio Vaccine Products entry (#516) for further information.

The Average Wholesale Price (AWP) is not available (not in Red Book, 2004 or 2005). The 2004 sales price reported by Walgreens was $233.09 for a 10-dose vial.