Immune Response
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Natural Exposure to Poliovirus

Once a poliovirus particle is able to gain entry into the intestines and infect mucosal epithelium M cells, they may be exposed to lymphocytes within the intraepithelial pocket. The activation of the mucosal immune response results in preferential expression of integrins and cell adhesion molecules associated with the homing of lymphocytes to mucosal sites of infection. Natural exposure to antigens on mucosal surfaces elicits secretory IgA antibody responses locally and at distal sites by migration of committed IgA-producing lymphocytes from Peyerís Patches to the mucosal lamina propria. While both humoral and cell-mediated immune responses have been associated with poliovirus infection, the antibody response is considered necessary in order to induce the immune state. A cytotoxic response is insufficient to clear an infection, but that does not exclude it from playing a role in an effective immune response. IgA antibody is present in the mucosal secretions and as a firmly adherent layer on the surface of the mucosal epithelial cells, thus shielding them from viral penetration. IgA, which exists as a homodimer in the mucosa, is able to bind to the capsid of poliovirus and neutralize it. Polioviruses that escape the mucosal immune response are able to spread into the circulatory system, where they are susceptible to serum neutralization by IgG antibody. Natural exposure without clinical evidence of disease is associated with increased levels of IgA and IgM. When clinical evidence of disease manifests itself, increased levels of IgM are usually found. This observation supports the belief that IgM doe not play a major role in the development of an effective immune response. Three distinct antigenic sites exist on each of the poliovirus capsid proteins VP1, VP2, and VP3. However, most of the neutralizing epitopes are located on VP1. Immunity involves the production of memory cells and is long lasting, evident by the rapid production of antibodies after restimulation of the immune response by live poliovirus. Repeated contact with circulating vaccine virus may be important in causing intestinal reinfection and boosting local and humoral immunity. Priming of the immune memory cells may also be elicited by cross-reacting antigens from other enteroviruses.

Vaccination Against Poliovirus

Vaccination with either IPV or OPV is associated with the production high titers of serum or circulatory IgG antibody to poliovirus. Both vaccines induced neutralizing IgG antibody to the whole virus, IgG antibody to VP1 and VP3, and similar secretory IgA antibody to VP1 and VP2 in the nasopharyngeal secretions (NPS) without any VP3 response. Antibody response to VP2 and VP3 may be short lived. The peak concentrations are normally observed after four doses of vaccine. Both vaccines have been associated with effective serconversion rates and paralytic poliomyelitis prevention.

IPV primary route of action is through the activation of the immune system to produce serum or circulating IgG antibodies against poliovirus. Serum antibodies to poliovirus are unable to limit primary viral replication in the mucosal epithelium. However, they have been shown to prevent CNS invasion by poliovirus by neutralizing polioviruses that have entered the circulatory system, effectively protecting vacinees from poliomyelitis. IPV has also been known to induce specific IgA antibodies, conferring gastrointestinal immunity to a certain extent. However, E-IPV still allows higher levels of shedding in stool for longer periods than OPV when vacinees are challenged with live virus. Immunization with IPV has been shown to induce antibodies that begin to decline after vaccination but persist at low levels for a prolonged period. IgG antibody levels plateau relatively quickly and remain high years after immunization while IgA levels slowly increased. IgM displayed a drop in titer over time. OPV shows the same general trend in antibody proliferation over time with the exception of inducing higher IgA titers.Ý IPV has also been shown to confer herd immunity at a level equal to that of OPV. IPV immunization is associated with enhancement of secretory IgA response to poliovirus in nasopharynx that results in a marked reduction in viral nasopharyngeal excretion. Such a response may limit pharyngeal spread of poliovirus among community members. It has been suggested that pharyngeal shedding is a result of secondary viral localization from the blood. The fact that IPV is able to induce neutralizing serum antibodies would explain the prevention of pharyngeal shedding of poliovirus with IPV.

OPV is able to induce both a serum IgG and secretory IgA antibody response. The IgA response is much more pronounced after immunization with OPV than with IPV. The immune response to OPV resembles that of natural infection. Although OPV decreases fecal shedding of poliovirus, gastrointestinal immunity induced by OPV can be overcome by a sufficient dose of challenge virus. IgA induced after OPV may be directed against epitopes not available with IPV vaccine because of the proteolytic effects of intestinal enzymatic environment.

References

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Onorato et al Mucosal immunity induced by enhance-potency inactivated and oral polio vaccines. J Infect Dis. 1991 Jan;163(1):1-6.

Zhaori, G Nasopharyngeal secretory antibody response to poliovirus type 3 virion proteins exhibit different specificities after immunization with live or inactivated poliovirus vaccines. J Infect Dis. 1989 Jun;159(6):1018-24.

Zhaori, G et al Characteristics of the immune response to poliovirus virion polypeptides after immunization with live or inactivated polio vaccines. J Infect Dis. 1988 Jul;158(1):160-5.

Mahon BP, Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor. J Exp Med. 1995 Apr 1;181(4):1285-92.

Triki, H et al Influence of host related factors on the antibody response to trivalent oral polio vaccine in Tunisian infants. Vaccine. 1997 Jul;15(10):1123-9.

Ogra, PL Comparative Evaluation of Immunization with Live Attenuated and Inactivated Poliovirus Vaccines. Annals New York Academy of Sciences, 1995 754 97-107

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Van Wezel, AL Inactivated poliovirus vaccine: current production methods and new developments. Rev Infect Dis. 1984 May-Jun;6 Suppl 2:S335-40.

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Kaul D, Ogra PL Mucosal responses to parenteral and mucosal vaccines. Dev Biol Stand 1998;95:141-6

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