Organizations involved (historically):

Children’s Hospital (Boston) – R&D; Tech.

Children’s Hospital (Cincinnati) – R&D; Tech.

University of Pittsburgh – R&D; Tech

National Foundation for Infantile Paralysis – R&D

Wistar Institute – R&D; Tech.

Connaught Laboratories, Ltd. – R&D; Tech

University of Toronto – Parent

Cross ref: See the entries below for poliovirus vaccines, both live and inactivated.

Description: Polio vaccines are used for prevention of poliovirus infection, which can lead to serious neurological disease including paralysis. Two types of vaccines are available – live oral poliovirus vaccine (OPV), which is being phased out in the U.S., and inactivated poliovirus vaccine (IPV) administered by intramuscular injection. From 1965 until recent years, OPV (Sabin-type vaccine) was primarily used in the U.S. for routine childhood immunization. Both IPV and OPV are comparably effective for preventing polio. However, OPV is associated with vaccine-associated paralytic poliomyelitis (VAPP), due to the live virus infrequently mutating or reverting back to neuro-virulence. OPV has continued to be used, particularly in lesser developed countries, because it is less expensive than IPV and offers increased protection against polio epidemics and ease of use (oral administration).

Both inactivated and live virus vaccines have been and continue to be marketed and used in the U.S. and worldwide. However, with the successful vaccination of most of the world’s population, wild poliovirus is becoming rare. Polio has become so rare that VAPP cases attributed to reversion to pathogenicity of live virus in persons having received live oral poliovirus vaccine (OPV) now outnumber cases of wild-type virus infection in the U.S. and most other countries. Since 1979, all cases of polio in the U.S. have been attributed to OPV, at a rate of about 1 case for every 2.4 million doses. Because of this and other reasons, the live OPV is being phased out in the U.S. and certain other developed countries in favor of IPV.

New monovalent type 1 oral poliovirus vaccines, targeted to current outbreak strains, are being used successfully in some countries experiencing reinfections/outbreaks. Vaccination with only type 1 virus vaccine alone has been shown to provide immunity in 80% after a single dose.

History: The limiting factor in the early stages of polio vaccine development was the lack of methods for culture of the virus. Dr. J.F. Enders, Childrens Hospital (Boston, MA), and collaborators (including T.H. Weller and F.C. Robbin) in the late 1940s developed human and monkey tissue culture technology enabling large scale culture of polio and other viruses, and observation and measurement of the cytopathic effect of poliovirus (allowing assay of viral titer); and received the Nobel Prize in Physiology or Medicine in 1954. The availability of penicillin, used to inhibit bacterial contamination of virus cultures, significantly contributed to enablement of polio virus cell culture.

In 1947, Dr. J. Salk, University of Pittsburgh, began investigating the poliovirus. He determined that there were three basic types of virus, and that a vaccine would need to protect against all of three types. Dr. Salk and colleagues developed cell culture methods that enabled development of inactivated vaccines in the 1950s. On July 2, 1952, Salk tried a refined inactivated vaccine on children who’d already had polio and recovered. After vaccination, polio-specific antibodies increased. He then tried it on volunteers who had not had polio, including himself, his wife and children. The volunteers all produced antibodies, with no significant adverse effects. Salk reported his findings in The Journal of the American Medical Association in 1953.

Nationwide testing of Salk’s inactivated polio vaccine (IPV) was launched in April 1954 with the mass inoculation of school children. The results were considered amazing – 60 to 70% prevention. However, some 200 cases of polio were caused by insufficiently inactivated vaccine, 11 people died, and all use/testing was halted. See discussion of the “Cutter incident” below. Higher production standards were adopted and vaccinations resumed, with over 4 million given IPV by August 1955. The impact was polio vaccination was dramatic, with 28,985 U.S. cases in 1955; 14,647 in 1956, 5,894. in 1957. By 1959, 90 other countries began use of IPV vaccine.

Connaught Labs. (Toronto, Canada) in 1954, then wholly owned by the University of Toronto, developed the Medium 199 (M-199; M199; Hank’s medium) culture medium used for the first large-scale manufacture of Salk’s inactivated polio vaccine.

Leadership and funding for polio vaccine development in the U.S. were provided by the Technical Committee, National Foundation for Infantile Paralysis (NFID), now the March of Dimes. NFID and U.S. polio vaccine development efforts concentrated initially on the Salk-type inactivated vaccine, while the World Health Organization (WHO) and others outside the U.S. concentrated on live oral vaccines. NFID conducted a clinical trial in 1954 using Salk’s inactivated poliovirus vaccine in 650,000 children, including 200,000 children in the placebo control group. Starting with approval of inactivated vaccines [Polio Vaccine Inactivated (Monkey Kidney Cell)] from Cutter Labs. (Miles/Bayer) and Merck Sharp & Dohme, the NFID sponsored mass vaccination programs in the U.S. With the later U.S. approval of oral vaccines, vaccination became as simple as eating a virus-laden sugar cube or a squirt of liquid into the throat, and nearly universal U.S. vaccine coverage using both vaccines was attained by the 1960s.

Dr. A. Sabin, Children’s Hospital (Cincinnati, OH), is generally attributed as the developer of OPV. Dr. H. Koprowski, Wistar Institute, and collaborators developed the first live OPV tested in humans in 1948. Dr. Sabin, did not consider Salk’s killed-virus vaccine as being potent enough, and wanted to mimic actual infection using a weakened form of the live virus. He experimented with more than 9,000 monkeys and 100 chimpanzees before isolating a rare form of poliovirus that would reproduce in the intestinal tract but not in the central nervous system. Clinical trials with this oral polio vaccine (OPV) began in 1957, and it was tested in other countries, including the Soviet Union and Eastern Europe. In 1958, other researchers tested an OPV in the U.S. and tried to cast doubts on Sabin’s “communist vaccine.” In spite of this, OPV was licensed in 1962 and quickly became the vaccine of choice. It was cheaper to make and easier to take than Salk’s injectable vaccine.

Companies previously approved for manufacture of Poliovirus Vaccine Inactivated (Monkey Kidney Cell) or IPV were Cutter/Miles/Bayer Corp. (April 1955-Dec. 1978); Merck & Co., Inc. (April 1955-July 1980); Parke-Davis Div., Warner-Lambert Co. (April 1955-July 1980); and Connaught Labs. Ltd. (now Sanofi Aventis Ltd.) (Jan. 1963-Nov. 1987; see entry below). Only one IPV vaccine is currently marketed in the U.S. Poliomyelitis Vaccine Adsorbed was manufactured (and marketed) by Parke-Davis Div., Warner-Lambert Co. (Oct. 1960-July 1980).

Besides the current manufacturer (Wyeth/Lederle), only one other company has ever received U.S. approval for manufacture of Poliovirus Vaccine Live Oral Trivalent or OPV – Pfizer Ltd. (est. no. 0338) was licensed from Oct. 1966-June 1979. Pfizer was licensed to manufacture the components: Poliovirus Vaccine Live Oral Type 1 from Aug. 17, 1961-June 12, 1979; type II from Oct. 27, 1962-June 12, 1979; and type III from March 27, 1962-June 12, 1979. A new OPV was recently approved as a component of a combination vaccine.

In 1960, Merck Sharp and Dohme reported evidence of a previously unidentified virus, now known as simian virus-40 (SV40; SV-40) in marketed inactivated polio vaccines. SV40 is tumorigenic in rodents and SV40 DNA has been detected in human tumors, including ependymomas, osteosarcomas, and mesotheliomas. SV40 is relatively resistant to formalin/formaldehyde inactivation. Merck discovered SV40 contamination just as the company was about to introduce a new and improved version of its Purivax inactivated poliovirus vaccine (IPV). Merck suspended shipment and withdrew its newly approved vaccine, even though federal authorities and committees in 1961 determined that there was as yet no evidence of harm from SV40 in vaccines. Shortly thereafter, it was discovered that the virus was oncogenic (cancer-causing) in hamsters. Millions of people had already received contaminated vaccine in the U.S. and even more in mass vaccination programs in the USSR and elsewhere.

IPV stocks used between 1955 and 1963 and possibly the oral polio vaccine (OPV) used in clinical trials between 1959 and 1961 were contaminated with SV40. The source of this virus was the macaque kidney cells used for virus culture. It was known at the time that this virus could cause tumors in laboratory rodents, and the discovery that this was in polio vaccines, particularly IPV, caused controversy involving the manufacturers, public health officials, and the Division of Biological Standards (DBS), NIH, the precursor of what is now the Center for Biologics and Research (CBER), FDA. Sub-sequent studies have shown that this large-scale exposure of the population to SV40 has not resulted in apparent adverse effects, e.g. rates of mesothelioma remained stable or decreased between 1975 and 1997. However, many aspects of the assessment of risks from SV40 and other primate retroviruses remain controversial and not conclusively resolved. Note, SV40 contamination is not an issue with the current U.S. IPV.

Researchers from the National Cancer Institute (NCI, NIH; Bethesda, MD) reported in the Jan. 28, 1998 issue of the Journal of the American Medical Association results from a large epidemiological study finding that live simian virus 40 (SV40) retrovirus contamination of the inactivated poliovirus vaccines used in the U.S. from 1963 to 1995 was not associated with an increase in cancer rates among vaccine recipients. Tens of millions of Americans received SV40 contaminated monkey kidney cell cultured poliovirus vaccine inactivated with formalin (formaldehyde solution) between 1955 and 1963. By 1961, 80%-90% of those under the age of 20 in the U.S. had received the vaccine. The investigators concluded, “After more than 30 years of follow-up, exposure to SV40-contaminated poliovirus vaccine was not associated with significantly increased rates of ependymomas and other brain cancers, osteosarcomas, or mesotheliomas in the U.S.”

In July 2004, researchers at Loyola University Medical Center reported finding SV40 contamination of monkey cell cultured live OPV manufactured in the former Soviet Union (USSR) for nearly 20 years starting in 1963, and distributed throughout the USSR, Eastern European countries, and Asia and Africa, including China (PRC) and Japan. Hundreds of millions received the vaccine and were exposed to SV40. SV40 virus was found in two out of three stored samples of live Soviet vaccines, but there was no infectious poliovirus in the third sample, indicating that the sample had degraded. Testing of the Soviet method used for inactivation of SV40, addition of magnesium chloride, was found only 95% effective. SV40 contamination of Soviet OPV ended in 1981 with adoption of a host cell line free of SV40 provided by the World Health Organisation (WHO).

Some critics have called for a halt in the continued use of monkey kidney tissues for manufacture of polio and other vaccines, due to concerns about contaminating primate retroviruses, e.g., SV40. The live oral poliovirus vaccines introduced in the U.S. since 1963 and currently marketed OPV have not been found to contain SV40 or other human retroviruses.

The attenuated virus in OPV can cause paralytic polio due to unchecked infection in immune compromised, e.g., AIDS, patients. Available studies indicate that Orimune, the only OPV currently marketed in the U.S., does 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 poliovirus strains in the vaccine are shed in the vaccinee’s feces for up to 6-8 weeks after administration and shed via the pharyngeal route for 1-2 weeks after administration. During this time household and other persons coming into oral contact with shed virus may also become infected with the vaccine strains.

Inadequately rigorous inactivation of some lots of inactivated polio vaccine by Cutter Labs (Berkeley, CA; later a subsidiary of Miles Labs., now Bayer Schering Corp.; ) shortly after initial approval in 1955 resulted in what has come to be known as the “Cutter Incident.” About 260 cases of polio and 11 deaths were linked to live virus contaminating what should have been an inactivated vaccine. Prior to approval, federal regulators and some in the scientific/medical community had expressed concerns about adequate inactivation, but public demand and the dire need for the vaccine contributed to its accelerated approval.

The development of OPV has been linked by some to the advent of HIV and the AIDS pandemic. For example, see The River: A Journey to the Source of HIV and AIDS, by E. Hooper, published by Little, Brown, New York, 1104 pages, 1999, $35. This book and other sources have suggested that one or more lots of an OPV (CHAT type 1 strain attenuated poliomyelitis virus) field tested in the 1950s in central Africa were produced using virus cultured in chimpanzee (or sooty mangabey) kidney cells infected with simian immunodeficiency virus (SIV), with SIV subsequently mutating into HIV in the inoculated populations and initiating the ongoing HIV/AIDS pandemic. The proponents of this hypothesis cite a number of geographic and temporal associations between field trials of OPV conducted in Africa, particularly field trials in the Belgian Congo (now Zaire) using OPV prepared by the Wistar Institute (Dr. Kop-rowski, et al.) and the Pasteur Institute, and the later appearance of HIV/AIDS in much the same areas. See Koprowski, H., “AIDS and the Polio Vaccine” [letter], Science, vol. 257, p. 1024, Aug. 1992; and Plotkin, S.A., “Chat Oral Polio Vaccine Was Not the Source of Human Immunodeficiency Virus Type 1 Group M for Humans,” Clin. Infect. Dis., vol. 32, no. 7. p. 1068-84, April 2001. There is no physical evidence (e.g., contaminated vaccine samples) of any linkage between experimental OPV and HIV. More needs to be known about the passage histories of particular seed lots, vaccine pools and batches (particularly CHAT 10A-11), some of which have been alleged to have been manufactured on-site in Africa, and the use of different monkey species and culture methods by those involved. However, insufficient documentation and samples have survived and it seem that there will never be definitive determination about SIV/HIV contamination of these vaccines.

Multiple investigations and committees have found no linkage between OPV use in Africa and HIV/AIDS. Considerable genetic evidence shows that HIV (or its SIV precursors) existed in Africa decades before OPV vaccination programs. If there is any linkage between OPV and HIV, it is more likely to be related to the then common practice of reusing syringes and needles without sterilization in field clinics, potentially passing existing SIV, HIV, and/or other primate retroviruses among those having received OPV in the same clinics. None of the allegedly/potentially contaminated lots of OPV were ever approved or used in the U.S. Recent studies continue to disprove a link between OPV and HIV in Africa. For example, in the April 22, 2004 issue of Nature, the HIV strains that currently infects chimpanzees in the African regions where vaccination programs took place were shown to have very different genomes than SIV strains that evolved into HIV.

Rotary International has been a major supporter of international polio vaccination/eradication programs. Rotary is a co-leader of the eradication campaign, to which it has contributed $600 million and tens of thousands of volunteers.

Status: Polio vaccination is universally required in the U.S. and most countries worldwide. In the U.S., children generally are not allowed to enroll in school unless they have received a full course of vaccination with either live oral (OPV) or injected inactivated (IPV) vaccine.

Effective Jan. 1, 2000, the Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC), recommended an all inactivated polio vaccine (IPV) schedule for routine childhood polio vaccination in the U.S. All children in the U.S. should receive four doses of IPV at ages 2 months, 4 months, 6-18 months, and 4-6 years. This was expected to substantially eliminate the occurrence of vaccine--associated paralytic poliomyelitis (VAPP) in the U.S.

OPV is still recommended for childhood polio vaccination in the U.S. under four circumstances including: 1) mass vaccination campaigns to control outbreaks of paralytic polio (highly unlikely); 2) children who have never received any polio vaccine who plan to travel within four weeks to countries where polio is common. These children may get OPV for the first dose; 3) children whose parents do not accept the required number of injections. These children should get IPV for the first two doses of the polio vaccine series, but may get OPV for the third or fourth dose, or both; and 4) children with a life-threatening allergy to the antibiotics neomycin, streptomycin, or polymyxin B (in IPV), or people who have had a life-threatening allergic reaction to a dose of IPV. These people may get OPV instead.

Disease: Poliomyelitis is caused by poliovirus types 1, 2, or 3. It is primarily spread by the fecal-oral (enteric) route of transmission but may also be spread by the pharyngeal route. Poliovirus is highly contagious. Infected persons shed the virus in their feces, potentially contaminating water supplies, swimming pools, etc. The virus is ingested and multiplies in the throat and intestines. Symptoms generally appear 4-35 days after infection and include fever, fatigue, headache, vomiting, stiff neck, and muscle pain. Approximately 90-95% of polio-virus infections are asymptomatic. Rapid onset of asymmetric acute flaccid paralysis occurs in 0.1% to 2% (about 1%) of infections, and residual paralytic disease involving motor neurons (paralytic poliomyelitis) occurs in ~1 per 1,000 infections.

Prior to the introduction of inactivated poliovirus vaccines in 1955, large outbreaks of poliomyelitis occurred each year in the U.S. The annual U.S. incidence of paralytic disease was 11.4 cases/100,000 population. This declined to 0.5 cases/100,000 population by 1961, shortly after introduction of oral poliovirus vaccine (OPV). Incidence has continued to decline to its present rate of 0.002 to 0.005 cases per 100,000 population. Of the 127 cases of paralytic poliomyelitis reported in the U.S. between 1980-1994, 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 oral poliovirus vaccine (OPV).

Worldwide, there are an on the order of 250,000 cases of polio per year, mostly in developing nations where universal vaccination has been achieved. There were about 3,500 cases of polio reported worldwide in 1998, with the actual number of cases estimated at about ten times the reported cases. No cases of polio (not associated with OPV) have been reported in North America since 1991. Massive vaccination campaigns, generally using OPV, have taken place in most countries worldwide, starting in the 1950s in the U.S. and developed countries, and are still continuing in some lesser-developed countries. The need for polio vaccination is so well recognized that parties involved in wars and civil disturbances in lesser developed countries have called cease fires to allow national or regional vaccination days/campaigns.

Poliovirus only replicates in humans (i.e., humans are the only host), so vaccination of a large percentage of the population can eventually lead to total eradication (extinction) of the virus. Polio has been considered by many to be on track to become the second viral disease to be eradicated from the planet (other than laboratory samples) due to vaccination, with variola virus (smallpox) being the first. Since 1988, some 2 billion children around the world have been immunized against polio, involving the cooperation of more than 200 countries. Besides eliminating disease, eradication of the virus could lead to worldwide savings of about $1.5 billion associated with vaccination and treatment of cases. After the last case is reported worldwide, surveillance for the disease will continue for another five years before the World Health Organization (WHO) plans to declare the planet free of poliovirus. After that, vaccination efforts will be halted.

In Jan. 2004, the health ministers of the few countries still experiencing polio outbreaks (from lack of completion of universal vaccination), Nigeria, India, Pakistan, Niger, Egypt and Afghanistan, signed a declaration affirming their commitment to global polio eradication. However, problems in attaining this goal persist, e.g., the predominantly Muslim Kano regions of Nigeria has experienced difficulties and discontinued vaccination efforts after rumors and allegations by local Muslim religious leaders and others that the OPV being used was contaminated with HIV and could cause female infertility. Tests proved the rumors unfounded, but in the meantime polio had spread across Nigeria into previously polio-free countries, such as Chad, Ghana, Togo, Benin and Cameroon. Vaccination has resumed using vaccine manufactured in a Muslim country (from Bio Farma, Indonesia).

Poliovirus eradication (and associated halt in polio vaccination) will make future generations susceptible to polio epidemics, e.g., from biological warfare or bioterrorist use of poliovirus – a situation comparable to that with smallpox. With poliovirus being much more common and widely studied, compared to variola virus, it will be much harder, if not impossible, to assure complete destruction of all stored stocks of virus. Presuming polio vaccination is eventually halted after presumed eradication of the virus, like smallpox, the entire world’s population will be highly susceptible to poliovirus infection, making poliovirus very attractive as a biological warfare/bioterrorist weapon of mass destruction (comparable to smallpox). Also, many countries still are extensively using inexpensive live oral (OPV) for vaccination programs, which involves a low level of infections with mutant pathogenic poliovirus. Assuring virus eradication and the politics, economics, etc., of ending poliovirus vaccination will be highly complex. Eventually, after presumed virus eradication, decisions will need to be made whether to continue or halt universal vaccination, and if vaccination is halted whether stocks of vaccine will need to be stored for the world’s population (or for those countries that can afford it), much as the current situation with smallpox vaccines. With potential bioterrorists and state-sponsored biological warfare programs likely to retain wild poliovirus samples, e.g., now readily available in areas still experiencing outbreaks (with many of these same regions also known for terrorist activity), it may never be prudent to halt polio vaccination, as has been done with smallpox.

In 2007, the 19th year (since 1988) of the polio eradication effort based on vaccination of all (or nearly all infants), disease eradication remains an elusive goal. Polio is on track for eradication in Egypt, India and other countries. Massive immunizations have reduced the number of cases from 350,000 a year in 1988 to 1,255 cases in 2004. However, polio outbreaks persist in areas of Africa and Asia, e.g., Nigeria and Indonesia, where vaccination programs have not been fully effective. The World Health Organization (WHO) reports that between Jan. 2003 and July 2005, 18 formerly polio-free countries were reinfected with a strain that originated in northern Nigeria. Reinfection/outbreaks occur, because countries have not maintained adequate immunization rates in infants/young children.

Vaccination in many areas is made difficult by ignorance, erroneous rumors, superstitions, contrived allegations, and political manipulation. For example, in some predominantly Muslim areas in Africa and elsewhere, the vaccine has been associated with HIV/AIDS, incorporation of porcine components, infertility, and other false allegations. In 2005, WHO withdrew support for the oral polio vaccine (OPV) manufactured by Biofarma, an Indonesian state-owned company, and the only OPV manufactured by a predominantly Muslim country, further adding to suspicion of OPV in Muslim countries. Biofarma had previously provided 30% of the global oral polio vaccine supply. In Indonesia alone, where over 200 cases of infection have been reported, it is expected that upwards of 40,000 persons could be infected, given the 200-to-1 normal ratio of infections to paralysis.

In Oct. 2006, the World Health Organization (WHO) reported that success in eradicating polio depends primarily on four countries -- Afghanistan, India, Nigeria, and Pakistan. All children paralysed by polio in the world in the prior year were infected by virus originating in one of these four endemic countries. WHO authorities also noted that many developed (affluent) countries are likely to continue vaccinating children for polio even after the disease is eradicated, in part because of the threat of polio virus for bioterrorism/biological warfare (with samples readily available in the field in endemic countries and in laboratories worldwide).

No type 2 poliovirus infections have been detected since Sept. 1999. This strain appears to have been eradicated (so future vaccine formulations may not need a type 2 component). However, as with smallpox, eradication of a pathogen and halt of immunization, with no one having natural of vaccine-induced immunity, makes the pathoge a prime candidate for bioterrism/biological warfare use. With polio having more recently than variola virus been fairly common worldwide (available to those seeking to use it for bioterrism/biological warfare), it may not be prudent to halt vaccination for seemingly-eradicated polio strains.

Market: Polio vaccination is required for all children in essentially all U.S. states, e.g., for entrance into school. In July 2004, CDC estimated that in 2003 91.6% (±0.7%) of children in the U.S. aged 19-35 months had received four or more doses of a poliovirus vaccine.

In Nov. 2004, the Centers for Disease Control and Prevention (CDC) reported that polio vaccine coverage (the percentage of those vaccinated) among U.S. children entering school (kindergarten) in 2003-2004 was 95.6%.

Sanofi Aventis Inc. is currently the only supplier of IPV (IPOL) in the U.S. market. Polio vaccines currently account for ~5% of Sanofi’s human vaccine sales. As the aim of global polio eradication approaches, the importance of eliminating all pathogenic virus, including from reversion (mutation) of OPV, will increase, and the use of IPV vaccines like IPOL will increase worldwide. The company is expanding production capacity.

In Jan. 2007, researchers from Harvard School of Public Health reported that the U.S. has collectively saved $180 billion between 1955 and 2005 from its $35 billion expenditures for polio vaccines and making polio a universal, required vaccine. They estimated that historical and near-term future investments in polio vaccination translates into over 1.7 billion vaccinations, which have and will prevent ~1.1 million cases of paralytic polio and over 160,000 deaths This does not include less quantifiable benefits, like removing the stress of fear and the suffering that the disease (or the possibility of the disease) brings.

Market: In Dec. 2007, news stories reported that Salk (inactivated) vaccine costs (presumably for large internatiional and other major public health program purchasers) $2.70/dose, while live oral OPV cost about $.15/dose. This illustrates some of the cost-related challenges in switching all polio vaccination over to IPV. Illustrating the progress in eradicating polio, it was also reported that fewer than 900 cases had been reported in 2007, while over 350,000 cases with paralysis were reported before eradication efforts began in the late 1990s..

Competition: manufacturers of OPV internationally include Beijing Institute of Biological Products (China); P.T. Bio Farma (Persero) (Indonesia); Birmex (Mexico); Chiron Behring GmbH & Co. (Germany); Chiron SpA (Italy); Sanofi Pasteur (Canada); Institute of Poliomyelitis and Viral Encephalitides, Academy of Medical Sciences of the Russian Federation (CIS/Russia); Dong Shin Pharmaceutical Co. (Korea); Japan Poliomyelitis Research Institute (Japan); Peking Union Medical College (China); GlaxoSmithKline Biologicals (Belgium); Poliovac (Poliomyelitis Vaccine Research and Production Center) (Vietnam); and Razi Institute (Iran).

Internationally , manufacturers of IPV include Evans Vaccines Ltd. (Chiron Vaccines) (U.K.); GlaxoSmithKline Biologicals (Belgium); Japan Poliomyelitis Research Institute (Japan); SBL Vaccin AB (Sweden); Statens Serum Institut (Denmark); SVM (the Netherlands); and Institute of Immunology and Virology Torlak (Yugoslavia).

In March 2005, Monovalent Oral Polio Vaccine 1 (MOPV1) from Sanofi Pasteur received its first approval in France (allowing export of the vaccine to lesser-developed countries). The company specifically manufactured 50 million doses of this monovalent vaccine to be used in Egypt where poliovirus types 2 and 3 have been eradicated, but not type 1.

R&D: In May 2006, Nederlands Vaccin Instituut (NVI) formed a collaboration with Panacea Biotec Ltd. (PBL). NVI will supply bulk IPV for the manufacture of finished IPV and a number of IPV based combination vaccines. PBL will market the products both in India and across the globe, except for The Netherlands, Denmark, Norway and Finland.