During the twentieth century, many significant scientific advances were made which furthered the understanding of poliovirus. In 1949, poliovirus was grown by Enders on tissue culture, which paved the way for detailed research on the molecular biology of poliovirus. That same year, the virus was grouped into three immunological types, or serotypes. Subsequent to the discoveries of Avery et al and Hershey and Chase on DNA-mediated transformation of bacteria, RNA was identified as the infectious agent of poliovirus in 1957. Shortly thereafter, the basic steps of replication cycle of poliovirus were established, and the interaction of poliovirus with its antibody was analyzed. X-ray crystallographic and electron microscopic analysis of poliovirus contributed to its further characterization.

The Oral Polio Vaccine (OPV) was developed in 1958 by Dr. Albert Sabin. Sabin attenuated the wild type poliovirus by passaging the virus in monkey kidney epithelial cells. The commonly used form of the oral polio vaccine is trivalent, which means that it contains live attenuated strains of the three serotypes of poliovirus. Trivalent OPV is characterized in vivo by efficient growth properties in the intestinal tract, unaltered immunogenic properties with respect to wild type progenitors, and attenuated neurovirulence after experimental intraspinal injection into primates. This means that an individual immunized with trivalent OPV induces long-lasting (frequently life-long) protective immunity of the gastrointestinal tract to all known forms of poliovirus.

Once administered, the attenuated vaccine colonizes the intestine. This colonization enables the production of secretory IgA, which serves as an important defense against naturally acquired poliovirus, as well as smaller amounts of IgM and IgG. Since it is a polymer, secretory IgA can cross-link large antigens with multiple epitopes at mucous membrane surfaces, which are the main entry sites for most pathogenic organisms. The binding of IgA to viral surface antigens prevents the attachment of the pathogen to the mucosal cells, thereby inhibiting viral infection of the cells. Complexes of secretory IgA and antigen are entrapped by the mucous and eliminated by the ciliated epithelial cells of the respiratory tract or by the peristalsis of the gut.

Since the three attenuated strains of poliovirus present in the OPV interfere with each other's replication in the intestine, boosters of OPV are required to induce protective immunity to all three polio serotypes. In the first immunization, one strain will grow most effectively, and immunity to this strain will be induced. With the second immunization, the immune response generated to the first strain will inhibit the growth of that same strain, such that a second strain will replicate most successfully, inducing immunity to the second strain. Similarly, immunity is induced to the third strain with the third booster.

There are many biological and practical advantages to the Oral Polio Vaccine. Since attenuated vaccines are capable of transient growth, the OPV allows prolonged exposure of the immune system to the epitopes on the attenuated organisms, resulting in increased immunogenicity and memory-cell development. OPV also indirectly protects other susceptible individuals by secondary vaccination, which means that vaccinated individuals may spread the vaccine virus in the community and thereby inhibit the spread of the wild type virus if it occurs in the population. Significantly, OPV prevents the vaccinee from acting as a carrier of wild type poliovirus, and as stated, confers long-lasting immunity. The OPV is also easily administered by giving children a sugar cube or sugar liquid containing the vaccine, neither of which requires extensive medical training to be administered.

The most serious disadvantage of the Oral Polio Vaccine is the risk of vaccine-associated paralytic polio as a result of the vaccination. In fact, in any attenuated vaccine, there exists a danger that the attenuated form will revert to the virulent form. The Centers for Disease Control estimate that 1 case per 2.5 million doses of OPV distributed results in vaccine-associated paralytic polio, however, the risk increases significantly for the first dose of OPV, which results in 1 case per 790,000 doses administered. The risk is even higher for children receiving their first dose of OPV, as 1 in 520,000 children acquires vaccine-related polio after receiving their first OPV dose. Particularly problematic in Third World countries, other gastrointestinal viruses interfere with the replication of the attenuated polio vaccine viruses in the intestine of the vaccinees. Also, the fact that several boosters are required to induce protective immunity significantly decreases the success of polio vaccination programs, which is corroborated by studies that reveal that in Third World countries 20% of people fail to return for each subsequent booster.

Immunosuppressed individuals should not take the Oral Polio Vaccine, and should avoid contact with persons who have received the Sabin vaccine for two weeks post vaccination. This includes people with AIDS, HIV infection, other immunodeficiency diseases, cancer, leukemia, and lymphoma. People receiving radiation treatments, medications to treat cancer, corticosteroids (such as prednisone), or other immunosuppressive medications should also follow these recommendations. Should vaccination against polio be deemed necessary for these individuals, they should be vaccinated with IPV.

As the target year for the eradication of poliomyelitis approaches, the objectives of the World Health Organization is working to implement improved methods for identifying wild-type poliovirus and determining infection with poliovirus including:

1. Polymerase Chain Reaction to identify wild-type poliovirus in clinical specimens and environmental samples.
2. Nucleic acid hybridization to specifically identify all wild-type polioviruses.
3. Restriction fragments length polymorphism (RFLP).
4. Use of mouse cell lines expressing the human poliovirus receptor.
5. Use of Sabin-specific monoclonal antibodies for rapid identification of Sabin-related poliovirus by neutralization.
6. Development of a standard test for detection of poliovirus-specific IgM antibodies to evaluate transgenic mice as an animal model for neurovirulence test of oral poliomyelitis vaccine.

Current objectives guiding vaccine research and development include defining more efficient immunization strategies and new delivery systems. Improving immunization strategies means investigating approaches such as nucleic acid vaccines, combined vaccines, mucosal immunization, and neonatal vaccination. There is a major effort in polio research particularly to produce a DNA vaccine, in which genes from polio would be inserted into a bacterial plasmid. DNA vaccines successfully elicit an immune response, although the mechanism of this response is as yet undetermined. A potential risk of using DNA vaccines in humans is that injecting naked DNA might not be safe; this foreign DNA could insert itself into and damage human chromosomes and potentially increase the risk of cancers or autoimmune disorders.

As stated, multiple boosters of vaccine are required to induce immunological memory to all three serotypes of poliovirus. Ideally, children could receive a single vaccine to replace the current childhood immunization schedule, however, because of the antagonistic effects of various vaccines, this is not yet possible. Efforts are however underway to minimize the number of boosters required for polio immunization, and include research into the development of a single vaccine with a time-release mechanism.

Other possibilities to increase the efficiency of polio vaccination include using adjuvants, particularly to improve the mucosal immune response typically generated by OPV. Also, a vaccine that induced only a localized immune response would minimize tissue damage generated by processes such as innocent bystander lysis. The Children's Vaccine Initiative has also made substantial progress including the development of a heat-stable polio vaccine and a single-dose tetanus toxoid vaccine, which could prevent some 600,000 deaths per year

Viral DNA Vaccine Synthesis, Source: Kuby, 452.

The great success of the Sabin attenuate polio virus at providing effective protection at the mucosal surface stimulated interest that it might be used as a recombinant vector vaccine, that is, as a vector for foreign genes. It remains uncertain whether these foreign structures are sufficiently immunogenic to induce an adequate humoral response to the insert, since such structures do not productively replicate.