Poliomyelitis vaccine

Inactivated poliomyelitis vaccine

Inactivated poliomyelitis vaccine produced by improvements in manufacturing technology (potency-enhanced IPV-eIPV was licensed in 1987) is used for routine immunization in an increasing number of countries (for example in Finland, France, Germany, Iceland, the Netherlands, Norway, Sweden, and certain provinces of Canada) and is recommended in other countries for certain specific purposes, for example for persons with underlying immunological disorders or non-immunized adults exposed to high risk. A few countries (for example Denmark, Hungary, Italy, Lithuania, and Israel) use a mixed schedule, starting primary immunization with IPV followed by OPV.

The US 2000 childhood immunization schedule, proposed by the Advisory Committee of Immunization Practices (ACIP), the American Academy of Pediatrics, and the American Academy of Family Physicians, recommended an all-IPV schedule for routine use in the USA, aimed at the elimination of the rare vaccine-associated paralytic poliomyelitis [ ]. Since 1 January 2000, all children have received four doses of IPV at ages 2 months, 4 months, 6–18 months, and 4–6 years.

Some other industrialized countries that use OPV in their routine immunization programs, and which had no wild poliomyelitis cases for many years but some vaccine-associated poliomyelitis, are reassessing their immunization strategy. They are considering new concepts of shifting from OPV to IPV or from OPV to mixed schedules. This change could help to prevent vaccine-associated poliomyelitis mostly occurring after the first dose of OPV immunization.

Serious adverse reactions after IPV immunization have not been documented [ ]. Because IPV contains streptomycin and neomycin, there is a possibility of allergic reactions in those who are sensitive to these antibiotics. Although it has been postulated that IPV, like some viral infections, might trigger Guillain–Barré syndrome, there is inadequate evidence to accept or reject such an association [ ]; in this respect it may differ from the oral vaccine.

Oral polio vaccine

In contrast to IPV, OPV causes important problems, including vaccine-associated polio and prolonged polio virus excretion.

Combination vaccines

The safety, immunogenicity, and lot consistency of five-component pertussis combination vaccine (DtaP + IPV + PRP-T-Hib) in infants have been compared to those of a whole-cell pertussis combination vaccine (DTwP + IPV + PRP-T-Hib), as have separate and combined injections of DTP + IPV and Hib. The combination vaccine DtaP + IPV + Hib were comparable or superior regarding safety and immunogenicity to the combination vaccine containing the whole cell pertussis component. There was no interaction between acellular pertussis and PRP-T-Hib, a feature that distinguishes this combination vaccine from some others, which depress anti-PRP responses. The combination vaccine DtaP + IPV + Hib produced significantly lower rates of local and systemic reactions than did the combination vaccine containing the whole-cell pertussis component. Local reactions, such as redness, swelling, and tenderness occurred two to three times more often after combination vaccine containing whole cell pertussis than after combination vaccines with acellular pertussis components. Fever was three times more common after whole cell combination vaccine. Fever over 40 °C was rare in all vaccinees, because of the use of paracetamol prophylaxis. Systemic reactions, such as fussiness, crying, reduced activity, and anorexia, were about twice as frequent with whole cell vaccine as with acellular pertussis vaccine. Both local and systemic reactions persisted longer after whole cell vaccine than after acellular pertussis vaccine. There were no significant differences between reaction rates among infants given DtaP + IPV vaccine combined with PRP-T-Hib vaccine in the same syringe compared with those given separate injections, except for local redness after the first dose [ ].

Hexavalent immunization

The Hexavalent Study Group has compared the immunogenicity and safety of a new liquid hexavalent vaccine against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b (DTP + IPV + HB + Hib vaccine, manufactured by Aventis Pasteur MSD, Lyon, France) with two reference vaccines, the pentavalent DTP + IPV + Hib vaccine and the monovalent hepatitis B vaccine, administrated separately at the same visit [ ]. Infants were randomized to receive either the hexavalent vaccine (n = 423) or (administered at different local sites) the pentavalent and the HB vaccine (n = 425) at 2, 4, and 6 months of age. The hexavalent vaccine was well tolerated (for details see the monograph on Pertussis vaccines). At least one local reaction was reported in 20% of injections with hexavalent vaccine compared with 16% after the receipt of pentavalent vaccine or 3.8% after the receipt of hepatitis B vaccine. These reactions were generally mild and transient. At least one systemic reaction was reported in 46% of injections with hexavalent vaccine, whereas the respective rate for the recipients of pentavalent and HB vaccine was 42%. No vaccine-related serious adverse event occurred during the study. The hexavalent vaccine provided immune responses adequate for protection against the six diseases.

Polio vaccines as a possible cause of AIDS

There is a hypothesis that the HIV virus might have jumped the species barrier from monkey to people via a contaminated polio vaccine because the vaccine was manufactured in primary monkey kidney tissue known to be sometimes contaminated with monkey viruses. The existing evidence, including tests of poliovirus seed stocks, more than 20 vaccine lots, and serum samples from vaccine recipients makes this hypothesis highly improbable [ ].

Contamination of polio vaccines with simian papovavirus 40 (SV40)

The problem of early polio vaccines produced in the 1950s and early 1960s, and, in some instances, contaminated with the monkey virus SV40 (simian virus 40) has been discussed [ ]. From 1954 to 1962, millions of people were immunized with polio vaccines, which during that period contained SV40 as an unrecognized contaminant. Some studies sought to investigate possible causation between the receipt of the vaccine and the development of tumors, but the results were not convincing [ ].

Critical assessment of virological and epidemiological data suggests a probable causative role for SV40 in certain human cancers, but that additional studies are necessary to prove etiology [ ]. To help answer these issues, the World Health Organization has provided the following statement [ ]: “Investigations from several medical research institutions have detected the presence of simian virus 40 (SV40) genome in certain rare human tumors, notably mesotheliomas, osteosarcomas, and brain tumors. SV40, which is known to induce tumors in laboratory rodents, is a polyomavirus identified in 1960 as a contaminant of some batches of primary rhesus monkey kidney cells used to produce polio vaccine in the 1950s. Soon after its discovery, measures to exclude the virus from polio and other vaccines were rapidly introduced into WHO Requirements for the Manufacture and Quality Control of Polio Vaccines, and these have been rigorously applied by vaccine manufacturers. For over 30 years now, polio vaccines made in primary monkey kidney cells have been shown to be free of live SV40.”

The use of new and highly sensitive polymerase chain reaction (PCR) techniques for the detection of the SV40 genome in batches of oral polio vaccines from several manufacturers has confirmed that the measures taken have been effective in excluding SV40 from vaccines. There is no doubt that the early batches of polio vaccine that were used between 1955 and 1963 contained SV40. Epidemiological studies between 1960 and 1974 failed to show an association between exposure to SV40-contaminated vaccines and human tumors. More recent epidemiological data from tumor registers, involving more than 60 million person years of observation, have likewise found no differences in tumor incidence that could be attributable to SV40-contaminated polio vaccines. The latest data published in the Journal of the National Cancer Institute, USA, suggest that SV40 may be present in humans more commonly than had previously been thought, and raises the possibility of transmission of the virus among humans. Whether the antibodies that have been detected are due to exposure to SV40 or to cross-reacting human polyomaviruses is not known. Neither is it certain that SV40 strains now present in the human population originated from the use of the early polio vaccines. Despite almost 40 years of observation, there is still no evidence that SV40 contamination of some early batches of polio vaccine has had any adverse effect on human health.

The River by Edward Hooper

The hypothesis that oral polio vaccine played a key role in the current AIDS epidemic was raised again by Edward Hooper, who has worked many years for the BBC and the UN in Africa and some years ago wrote a book called “Slim,” in which he described the AIDS epidemic in East Africa. His book The River . A Journey to the Source of HIV and AIDS , published in 1999 [ ], raised great public attention and was discussed in BBC Press Releases and in the New York Times. Leading experts in virology and AIDS research published comments in Science and other scientific journals. “The River” is a thoroughly researched, well-written book and deserves to be taken seriously. Hooper carefully collected data and events describing the first phases of HIV infection and AIDS, as well as the early development and implementation of polio vaccines. His book reflects some hundreds of interviews, including the leading researchers in the related fields, and he has documented more than 4000 references.

The hypothesis is based on the following facts and assumptions. In 1957 and 1958, Koprowski, from the Wistar Institute in Philadelphia, was administering oral polio vaccine in Africa (pre-licensure field trials in Burundi, Rwanda, and the North-East Congo) near Stanleyville (now Kisangani) in Congo. Not far from the base, chimpanzees for use in medical research were housed in Camp Lindi and might have carried a primate immunodeficiency virus (PIV). Chimpanzee kidneys for hepatitis research were shipped from Camp Lindi to the Virological Department of the Children Hospital in Philadelphia in 1958 and 1959. Hooper suggests that “it could be that (kidneys from these chimpanzees) ended up at the Wistar”, the laboratory in Philadelphia where polio vaccines were manufactured, where they contaminated vaccines with PIV. The polio vaccine that was supposed to be contaminated with PIV was then used in the Congo, transmitting the virus that evolved into HIV-1, the starting point of the worldwide HIV-1 epidemic. Over the next 20 years, infected humans progressed to AIDS, and the disease became visible in central Africa in the mid-to-late 1970s.

Does Hooper prove his hypothesis beyond a shadow of doubt? No, but he makes a powerful case for soberly and squarely addressing the issue.

There are also strong arguments against the hypothesis. Polio vaccines were first propagated in kidney cultures of rhesus and cynomolgus macaques, and later in African green monkeys. Plotkin and Koprowski categorically stated in a letter to the editor of the New York Times (7 December 1999) that no chimpanzee tissues were used in the Wistar Institute for polio vaccine production. They added that two independent analyses of the probable timing of the crossover of HIV from chimpanzees into humans give dates earlier than 1957–59, the years in which the Wistar polio vaccine was used in the Congo [ ]. It should also be mentioned that the vaccine manufactured in Wistar at that time was not only used in Africa but also in Sweden, Poland, and the US. One vial of Wistar’s oral polio vaccine stored in Stockholm has already tested negative. Garrett and colleagues in England experimentally examined the survival of human and simian immunodeficiency viruses in oral polio vaccine formulations; no live retrovirus came through the procedure. Wistar declared that they would release lab specimens from a polio vaccine project carried out at the end of the 1950s in Africa for examination in two independent laboratories, in order to dispel claims that Wistar scientists inadvertently caused the AIDS epidemic.

It should be mentioned that the majority of scientists believe that the AIDS epidemic began after the simian immunodeficiency virus was transmitted from chimpanzees to humans during the slaughter of chimpanzees as early as the 1930s [ ].

Finally, it is worth repeating the statement of the US Centers for Disease Control and Prevention, issued in 1992 but still valid [ ]: “The suggestion that HIV, the AIDS virus, originated as a result of inadvertent inoculation of an HIV-like virus present in monkey kidney cell cultures used to prepare polio vaccine is one of a number of unsubstantiated hypotheses. The weight of scientific evidence does not support this idea and there is no more reason to believe this hypothesis than many other which have been considered and rejected on scientific grounds.”

Nevertheless, there are important lessons to be learned from Hooper’s book. For many years, virologists and regulatory authorities have been worried that using permanent cell lines for vaccine virus propagation may somehow transfer cancer-causing properties and animal viruses. African green monkey kidneys are still used as the main cell substrate for oral polio vaccine. Millions of doses have been made from simian immunodeficiency virus (SIV)-positive monkeys before screening was introduced. Now there are well-tested non-oncogenic cell substrates, and it is time to reopen the debate on the use of primary cells versus cell lines for live attenuated virus vaccines. There is also a need to strengthen research on the sources of AIDS. However, the main focus of AIDS research should be prevention and treatment.