Live Oral Poliovirus Vaccine Research Articles

The Humoral Immune Response to Type 1 Oral Poliovirus Vaccine in Children Previously Immunized With Enhanced Potency Inactivated Poliovirus Vaccine or Live Oral Poliovirus Vaccine

Sixty-one children who had previously received three doses of enhanced potency inactivated poliovirus vaccine (epIPV) at 2, 4, and 18 months of age and 56 children who had previously received oral poliovirus vaccine (OPV) according to the same schedule were challenged with a single dose of monovalent, type 1 oral poliovirus vaccine (OPV1) between 19 and 52 months of age. Before the OPV1 challenge, the previously epIPV-immunized recipients had a geometric mean poliovirus type 1 microneutralization antibody titer (geometric mean titer [GMT]) of 11.1 IU, which was significantly higher than the prechallenge GMT of 2.2 IU among the children who had previously received OPV. Three weeks after the OPV1 challenge, the GMTs for the epIPV-immunized recipients and the OPV-immunized recipients were 35.3 IU and 5.1 IU, respectively. For the epIPV-immunized recipients, both the prechallenge GMT and the postchallenge GMT were dependent on the D antigen content of the vaccine that they had previously received. A fourfold or greater rise in poliovirus type 1 antibody occurred after the OPV1 challenge in 50.9% of the epIPV-immunized children and in 28.6% of the OPV-immunized children; this difference was statistically significant. For both groups, antibody boosts were inversely correlated with the pre-challenge serum antibody titer. However, the epIPV-immunized children consistently were more likely to boost than the OPV-immunized children at equivalent levels of prechallenge antibody. This experience indicated that OPV1 administration effectively raises the level of serum antibody in children previously immunized with three doses of epIPV, especially in children with lower levels of preexisting antibody. This booster response was superior to the booster response of children who received three doses of OPV.

CONGENITAL MALFORMATIONS AND ORAL POLIOVIRUS VACCINATION DURING PREGNANCY

In February, 1985, mass vaccination with live oral poliovirus vaccine (OPV) was started during a poliomyelitis outbreak in Finland. Pregnant women were advised to take the vaccination. Judged as the rate of reported malformations, OPV during early pregnancy had no harmful effects on fetal development.

Vaccine-associated poliomyelitis in a household contract with Netherton's syndrome receiving long-term steroid therapy

Paralytic poliomyelitis developed in a man 51 days after his two-month-old daugther received her first dose of trivalent live oral poliovirus vaccine. The patient was receiving long-term glucocorticosteroid therapy (tapered to 12.5 mg per day for the eight months prior to his poliomyelitis) for Netherton's syndrome, a congenital syndrome characterized by bamboo-like hair, hyperkeratotic and hyperhidrotic skin, and multiple allergies. The patient was ventilator-dependent and quadriplegic throughout most of his hospital stay and died in the hospital 10 months after the onset of paralysis. “Vaccine-like” type 3 poliovirus was isolated from a stool specimen and his serum showed a significant rise in neutralizing antibody titer against type 3 virus. This case report represents the first documented case of vaccine-associated poliomyelitis in a household contact receiving glucocorticosteroids, although evidence of immunosuppression was not documented. Nevertheless, the case reinforces current recommendations not to administer oral poliovirus vaccine to persons known to be immune deficient or suppressed or to normal persons with close contacts known to be immune deficient or suppressed.

Different secretory IgA antibody responses after immunization with inactivated and live poliovirus vaccines.

The influence on secretory IgA antibody levels in milk and saliva of vaccination with oral, live poliovirus vaccine ( OPV ) and inactivated poliovirus vaccine (IPV) was studied. IPV, especially the antigen-rich Dutch vaccine, more often induced increases in antibody titers in milk (50%) than did OPV (26%) (P less than .01). OPV more often decreased the antibody levels in milk (40%) than did IPV (10%) (P less than .01). It was striking that mainly high prevaccination titers were decreased. The increases of IgA antibody in saliva were less striking. IPV caused increases as often in milk as in saliva, whereas OPV more often induced increases in IgA antibody in saliva, but there was a poor correlation between the changes in antibody titers in milk and those in saliva.

Immunization with Oral Poliovirus Vaccine in China

China began to produce oral, live poliovirus vaccine ( OPV ) in 1960. During 1960-1964, OPV was introduced in major cities only and subsequently was used throughout the country. Since that time the incidence of poliomyelitis has dropped dramatically, and the percentage of the healthy population with antibody has clearly risen. Data from many observations showed a high rate of isolation of other enteroviruses in the healthy population and in individuals with poliomyelitis. These findings indicate that some paralytic cases may be caused by other enteroviruses. Localized outbreaks of poliomyelitis still occur, however, and their elimination will require a campaign to ensure that greater than 90% of susceptible individuals are immunized.

The standardization of vaccines: a discussion.

Many changes have been made in the World Health Organization's (WHO) requirements for the production and control of both the killed and live (oral) poliovirus vaccines since their initial formulations in 1959 and 1962, respectively. The major changes in the production of killed vaccine concern the cell substrates used from primary tissue to passaged primary tissue or even a continuous cell line such as Vero. It has been shown also that there is no longer the necessity to test for residual infectious virus by the inoculation of monkeys, since cell cultures are much more sensitive for this purpose. For the live vaccine, a more uniform test for the titration of virus content has been introduced. Furthermore, international agreement on the details of the test for neurovirulence in monkeys has been reached. The expression of the immunogen of poliovirus in eukaryotic cells has been achieved, but whether it becomes a commercial proposition replacing one or both of our present vaccines remains to be seen.

Live attenuated oral poliovirus vaccine.

During 1952-1954, some of the first papers were published on the attenuation of wild poliovirus for vaccine purposes. These efforts soon came to fruition , and large-scale field trials were held in many countries under a variety of conditions. Routine use of live oral poliovirus vaccines ( OPV ) was begun in many countries during the spring of 1960, and vaccines made from the Sabin strains were licensed in the United States in 1961-1962. In the early years of immunization with OPV , vaccines were usually monovalent, but a trivalent vaccine is now used. Throughout the world the introduction and continued proper use of OPV has been followed by a striking decrease in the number of paralytic cases. This dramatic and persistent outcome has stimulated recent discussions on the possible eradication of the disease. This paper reviews the criteria for the selection of vaccine strains that now make up the OPV , thermal stabilization of OPV , safety precautions that are followed in the manufacture of OPV , genetic stability of OPV strains following replication in vaccines and their contacts, and potential incorporation into OPV of totally attenuated polioviruses that can no longer revert to neurovirulence because the regions of the viral genome associated with neurovirulence are deleted or altered.

Control of Poliomyelitis: A Continuing Paradox

Worldwide control of poliomyelitis efforts have encountered numerous complexities and problems. Although the disease has been eradicated from many geographic areas over the past 25 years it continues to defy control efforts in many tropical countries. This article describes the epidemiology and pathogenesis of polio infection and the mechanisms by which the 2 different vaccines inactivated poliovirus vaccine (IPV) and attenuated live oral poliovirus vaccine (OPV) induce protection against paralytic poliomyelitis. Oral vaccine take rates have been as low as 60% in tropical and semitropical areas in contrast to the almost 100% response characteristic in children in temperate climates. This problem appears to reflect a complex of anatomic physiologic and biochemical changes that accompany malnutrition associated with high rates of intestinal infection and diarrhea. The profound alterations of metabolic and immunologic mechanisms that result from repeated infection may produce a chronic state of imbalance. Lameness surveys in subtropical countries have indicated prevalence rates of residual paralysis in the 5-7/1000 range. OPV is currently being used in the Pan American Health Organization Expanded Program on Immunization and a saturation approach to immunization has been effective in countries such as Cuba. There is some evidence that in densely populated areas with constant introduction and circulation of virulent poliovirus a combined OPV-IPV schedule may be necessary to suppress the disease. Recombinant DNA technology should make it possible to construct safe nonvirulent strains of poliovirus vaccine that have the immunogenic advantages of live replicating viruses without the potential to undergo reversion and cause disease. In the interim it is essential that surveillance of cases and immunity levels of target populations continue.

Chronic Progressive Poliomyelitis Secondary to Vaccination of an Immunodeficient Child

We investigated an immunodeficient child in whom chronic progressive poliomyelitis developed after she had received live oral poliovirus vaccine. Poliovirus, Type II, was isolated from throat and stool during life and from several sites within the brain at autopsy. The brain isolate was classified as vaccine-like on the basis of temperature sensitivity and antigenic markers. However, in the monkey neurovirulence test, the brain isolate produced moderately severe lesions throughout the spinal cord and brainstem and appeared nonvaccine-like. Thus, the brain isolate demonstrated a dissociation between the antigenic and neurovirulence markers. Our observations suggest that, under unusual circumstances, such as immunodeficiency, attenuated poliovirus can produce a chronic progressive neurologic disease. This case also emphasizes the need to diagnose immunodeficiency as early as possible, so that live-virus vaccines will not be administered.

Immunization "dyspractice": The need for "no fault" insurance

We are on a collision course in many areas of the United States. A number of states have passed compulsory immunization laws for school children, yet the majority of the vaccines required in fulfillment of these laws have a specific incidence of adverse reactions. These range from mild fever or irritability to encephalitis or paralysis. True, the incidence is small, but it is real. For live oral trivalent poliovirus vaccine, for example, the package insert cautions that "the possible low level of risk to the vaccinated subject or to close contacts [should] be considered at all times." Yet what recourse does the one person in tens of thousands suffering an adverse reaction have?

Live oral poliovirus vaccine, type 3.

To the Editor.— Early fears that live oral poliovirus vaccine, monovalent type III might produce disease in the young adult group have not been borne out in the military population. The US Army has administered type III live oral poliovirus vaccine to more than 3.5 million young adults since 1963. The vaccine initially used was monovalent, given four to six weeks after type I monovalent vaccine in either one of two schedules. Since 1966 trivalent oral poliovirus vaccine has been given either as two doses eight or more weeks apart or as two doses four weeks apart followed by a third dose eight or more weeks later. Since June 1964, no cases of paralytic polio have been reported in US Army personnel. During this same period several hundred thousand adult military dependents also received the vaccine. No vaccine-associated cases have been reported to us from among this group. Therefore, it

Surveillance of Paralytic Poliomyelitis in the United States

In 1966, 103 cases of paralytic poliomyelitis were reported in the United States. An outbreak of 66 cases caused by type 1 poliovirus occurred in Texas, predominantly in unimmunized, preschool children. In 1967, 40 cases were reported, with 16 in southwestern border states. In both years, sporadic cases of poliomyelitis continued to occur in persons without known contact with either live oral poliovirus vaccine, or with other patients. During the three-year period 1965-1967, eight cases of paralytic poliomyelitis occurred in recent recipients of oral poliovirus vaccine, while 16 additional cases were reported in persons with familial or other close contact with vaccine recipients. In view of the proven benefit of oral poliovirus vaccines, however, these cases present a minor public health problem.

Effect of Sabin Poliovirus Vaccine on Incidence of Poliomyelitis in Italy

Extensive use of poliomyelitis vaccine (Salk) from 1958 to 1963 did not prevent the annual occurrence of thousands of paralytic cases of poliomyelitis in Italy. After the mass use of live oral poliovirus vaccine (Sabin) early in 1964, the number of reported cases quickly dropped from an average of more than 3,000/year during the four years prior to the use of oral vaccine to 254 in 1965, 147 in 1966, 106 in 1967, and 87 in 1968, and at least a portion of the reported cases could not be confirmed as having been caused by polioviruses. Most of the remaining cases of poliomyelitis have occurred in the southern and island regions (1.17/100,000 vs 0.08 in northern and 0.009 in central Italy in 1965; 0.68/100,000 vs 0.04 in northern, and 0.06 in central Italy in 1966) where the percentage of children vaccinated during the initial campaign and in the ongoing programs was, until recent compulsory vaccination legislation, much less than in the northern and central regions of the country.

Immunity of school children two years after oral poliomyelitis vaccination.

A serologic survey of the poliovirus immunity of children in a suburban school system was performed in 1964, two years after a mass oral vaccination program. Approximately 6% of the school children were studied and 96% had antibody titers of 8 or greater to all three types of poliovirus. Antibody levels declined during the two-year period, but only significantly so for types 2 and 3 in children who had not received a booster. Antibody titers to types 2 and 3 poliovirus in children who had been given a booster were significantly higher than those who had not received one. A single feeding of a trivalent live oral poliovirus vaccine resulted in a rise in antibody titer in slightly less than half of the subjects with low type 3 titers.

Immunity of School Children Two Years After Oral Poliomyelitis Vaccination

A serologic survey of the poliovirus immunity of children in a suburban school system was performed in 1964, two years after a mass oral vaccination program. Approximately 6% of the school children were studied and 96% had antibody titers of 8 or greater to all three types of poliovirus. Antibody levels declined during the two-year period, but only significantly so for types 2 and 3 in children who had not received a booster. Antibody titers to types 2 and 3 poliovirus in children who had been given a booster were significantly higher than those who had not received one. A single feeding of a trivalent live oral poliovirus vaccine resulted in a rise in antibody titer in slightly less than half of the subjects with low type 3 titers.

Poliomyelitis Associated With Type 2 Virus

Paralytic poliomyelitis was diagnosed clinically in a 29-year-old man three weeks after his 2-year-old son received trivalent live oral poliovirus vaccine. Type 2 poliovirus with "vaccine-like" characteristics was isolated from the patient's stool, and the serum showed a significant rise in neutralizing antibody against type 2 virus. There was no rise in complement fixation antibody titers. The patients illness was likely due to type 2 poliovirus contracted from his son. Physicians should inquire about the immunization status of parents before administering vaccine to children.

Paralytic Poliomyelitis In Unvaccinated Mother

To the Editor:— The letter by Dr. Edward B. Shaw (198:1224, 1966) regarding our article Vaccine-Acquired Paralytic Poliomyelitis in an Unvaccinated Mother (197:1034, 1966) prompts this reply. It was not the intention of the authors to discourage the use of live oral poliovirus vaccine. The initial sentence of the article stated clearly that the use of live oral poliovirus vaccine is responsible for the almost complete elimination of paralytic poliomyelitis. However, because the virus from the vaccine can be transmitted to persons handling the excreta of recently immunized infants, it is felt that parents and attendants should be protected by immunization with live oral poliovirus vaccine. The illness and the results of diagnostic virus studies support the diagnosis of paralytic poliomyelitis in the patient described. The patient's residual neurologic deficit was striking paralysis of the left upper and both lower extremities. In our judgment, the clinical course was

Vaccine-Acquired Poliomyelitis in An Unvaccinated Mother

<h3>To the Editor:—</h3> The paper, "Vaccine-Acquired Paralytic Poliomyelitis in an Unvaccinated Mother" (<b>197</b>:1034, 1966), has some disturbing implications, medicolegal applications which may be unfortunate, and certain defects of factual information on which conclusions are based. This report of a single case describes a paralytic illness involving, to a variable extent, all four extremities of a 43-year-old mother whose infant had been given trivalent, live oral poliovirus vaccine 22 days before the onset of her symptoms. The course of disease was compatible with the diagnosis of poliomyelitis, type II virus was isolated from the patient's stool specimens, and her antibodies against type II virus rose from 1:20 on the ninth day of disease to 1:80 on the 32nd day. The clinical picture is similar to poliomyelitis in many respects and naturally caused suspicion that exposure to the vaccinated child might have been the source of infection. Identification of the virus

Vaccine-Acquired Paralytic Poliomyelitis in an Unvaccinated Mother

LIVE oral poliovirus vaccine is responsible for the almost complete elimination of paralytic polio-myelitis.^1,2Henderson et al's¹data reveal the risk of paralytic poliomyelitis from live oral vaccine to vary according to the vaccine type and age of the recipient. The rate for type I vaccine is 0.17 per million doses administered; for type II, 0.02; and for type III, 0.4. In the older age group, especially for type III vaccine, the rate is 0.64 per million doses given. Dissemination of poliovirus occurs in close contacts following exposure to a recent vaccine recipient; however, cases of paralytic poliomyelitis acquired in such a manner have been exceedingly rare.

Vaccine-acquired paralytic poliomyelitis in an unvaccinated mother

LIVE oral poliovirus vaccine is responsible for the almost complete elimination of paralytic polio-myelitis.^1,2Henderson et al's¹data reveal the risk of paralytic poliomyelitis from live oral vaccine to vary according to the vaccine type and age of the recipient. The rate for type I vaccine is 0.17 per million doses administered; for type II, 0.02; and for type III, 0.4. In the older age group, especially for type III vaccine, the rate is 0.64 per million doses given. Dissemination of poliovirus occurs in close contacts following exposure to a recent vaccine recipient; however, cases of paralytic poliomyelitis acquired in such a manner have been exceedingly rare.