Poliovirus vaccination

INTRODUCTION — Immunization against poliovirus infection represents one of the world's great medical achievements. The last cases of naturally occurring wild type paralytic poliomyelitis in the United States occurred during a small outbreak due to type 1 poliovirus in an unvaccinated religious community in 1978 to 1979 [1].

As of January 2024, wild type 1 poliovirus (WPV1) remains endemic only in Pakistan and Afghanistan. Outbreaks caused by circulating oral polio vaccine-derived (cVDPV) type 2 strains now extend through much of sub-Saharan Africa, Pakistan, and Afghanistan, and in 2022 these strains were reported in certain localities of the United States, United Kingdom, and Israel [2-5].

Issues related to paralytic poliomyelitis, the post-polio syndrome, and global eradication of poliomyelitis are discussed separately. (See "Poliomyelitis and post-polio syndrome" and "Global poliomyelitis eradication".)

POLIOVIRUS VACCINES — Both inactivated poliovirus vaccine (IPV) and live attenuated oral poliovirus vaccine (OPV) were developed in the 1950s and have since been used worldwide for routine childhood immunization and to prevent and control polio outbreaks in endemic countries [6-8]:

●Since 2000, IPV is the only poliovirus vaccine available for routine infant and childhood immunization in the United States [9]. It is the preferred vaccine in most middle- and upper-income countries because it is safe, highly effective, incapable of causing vaccine-associated poliomyelitis (VAPP) and can be combined with other vaccines given by intramuscular injection.

●A combination of type 1 and 3 bivalent OPV (bOPV) vaccine and IPV is recommended by the World Health Organization (WHO) Expanded Program on Immunization (EPI) for routine infant immunization in low-income countries. In this context, IPV provides protection against disease caused by type 2 polioviruses and a boost in immunity to types 1 and 3. OPV vaccines are used for supplementary immunization activities in countries at increased risk of poliovirus transmission.

●Monovalent OPV vaccines for types 1, 2, and 3 (mOPV1, mOPV2, and mOPV3, respectively) are stockpiled by the Global Polio Eradication Initiative and deployed selectively in response to polio outbreaks [10]. A novel type 2 oral polio vaccine (nOPV2) was authorized for emergency use in countries at risk of circulating vaccine-derived poliovirus (cVDPV) type 2 transmission in November 2020, as further discussed below [11,12]. (See 'Monovalent OPV vaccines and nOPV2' below.)

Worldwide polio immunization practice has initiated a phased transition from OPV to IPV in anticipation of global polio eradication in the future, beginning with cessation of type 2 OPV use in April 2016 and the addition of IPV to the EPI schedule [13]. (See "Global poliomyelitis eradication" and 'Recommendations of the WHO' below.)

Inactivated poliovirus vaccine — IPV is prepared by inactivation of wild type or Sabin (OPV) strain polioviruses by treatment with dilute formalin [14-16]. IPV is combined with other infant vaccines including diphtheria-tetanus-acellular pertussis, hepatitis B vaccine, and Haemophilus influenzae type B vaccine in multivalent formulations for intramuscular administration in most upper- and middle-income countries. Standalone IPV vaccines are now included in infant immunization schedules in low-income countries that have replaced trivalent OPV (tOPV) with bOPV.

Immune response and efficacy — IPV seroconversion rates and antibody titers depend on the number of doses, the interval between doses, age at the first dose, and maternal antibody levels. In general, three doses administered at 2, 4, and 6 to 18 months of age are expected to induce seroconversion in >95 percent of infants [17,18]. A 6-, 10-, and 14-week schedule results in lower but effective seroconversion rates [18].

Detectable antibody persists at protective levels for at least five years, although geometric mean titers decline. In some cases, the level of antibody may fall below detectable levels over time, but persons who have previously seroconverted are likely protected by immune memory.

Fractional doses (equal to 0.2 times a full dose, delivered by intradermal or intramuscular injection) that mitigate the high cost of IPV have been adopted by India, Bangladesh, Sri Lanka, and Nepal. Dose per dose, fractional doses result in lower seroconversion rates than full doses but effectively boost pre-existing antibody titers [19-21].

The influence of primary IPV immunization on mucosal immunity is quite limited compared with OPV. However, IPV boosts both humoral and intestinal immunity in children who have previously received OPV [22]. In a trial including children in Sri Lanka (previously vaccinated with OPV) who received booster vaccination with a fractional dose of IPV or a full dose of IPV (administered intradermally), mucosal immunity was boosted to a similar extent in each group [23].

There have been few opportunities to assess the efficacy of current IPV vaccine formulations under conditions of natural exposure to wild type or cVDPV. A case-control study conducted following a type 1 poliomyelitis outbreak in Senegal in 1986 to 1987 found that one and two IPV doses administered to children provided 36 percent (CI 0 to 67 percent) and 89 percent (CI 62 to 97 percent) efficacy, respectively, against paralytic disease, albeit with wide confidence intervals [24]. Similarly, a study in Tamil Nadu, India, found that three IPV doses had an efficacy of 92 percent [25]. These efficacy estimates track observed seroconversion rates for one and two IPV doses, respectively [26].

Adverse effects — Transient local reactions (erythema, pain, induration) are comparable with reactions following a placebo injection [17]. With the exception of a single incident in which inadequately inactivated IPV from one manufacturer caused a serious outbreak of poliomyelitis shortly after initial licensure in the 1950s [27], there are no proven serious adverse events associated with IPV.

Live attenuated oral poliovirus vaccine — OPVs were developed by repeated passage of wild type polioviruses in primates and in cell culture [7].

OPV remains an important tool for control of poliovirus transmission in the developing world because of low cost, ease of administration, induction of mucosal immunity, and enhancement of household and population immunity by transmission of OPV viruses from OPV-vaccinated children to their nonimmune contacts [28]. A trivalent OPV formulation (tOPV) containing Sabin 1, 2, and 3 vaccine viruses was used worldwide until April 2016 when it was replaced with bivalent type 1 and type 3 OPV during a global synchronized switch [29]. Withdrawal of type 2 OPV was considered essential because type 2 wild polioviruses no longer circulate, and continued use of Sabin 2 viruses has been responsible for a disproportionate number of vaccine-associated paralytic poliomyelitis (VAPP) and circulating vaccine-derived poliovirus (cVDPV) cases [30]. Despite continued challenges, the strategic plan of the Global Polio Eradication Program calls for all OPV vaccination to cease and be replaced with IPV once all poliovirus transmission has been interrupted [31].

OPV vaccines are no longer licensed in the United States.

An optimal immune response to OPV requires multiple doses. When previously used in high- and middle-income countries, three tOPV doses given at least two months apart induced ≥96 percent seroconversion to all three types after the third dose [17], and detectable serum antibody to all three types persisted in 84 to 98 percent of vaccinees five years after primary immunization [32]. However, in some low-income countries, a series of tOPV doses at birth and at 6, 10, and 14 weeks of age induced lower seroconversion rates [33-37], averaging 73, 90, and 70 percent for types 1, 2, and 3, respectively [29].

Diarrheal disease and other enteropathies associated with poor sanitation inhibit replication of OPV vaccine viruses in the gastrointestinal tract and thereby limit the immune response. One study conducted in Brazil and the Gambia [29,38] and another one conducted in Bangladesh [39] showed that diarrhea reduced seroconversion rates to types 2 and 3 OPV, while the response to type 1 was not affected. The impact of diarrhea on seroconversion persists despite the administration of three or four trivalent OPV doses.

Bivalent type 1 and type 3 OPV — Bivalent type 1 and type 3 OPV vaccine (bOPV) is the only OPV routinely used for infant immunization worldwide. The absence of interference from type 2 poliovirus in the trivalent formulation leads to superior bOPV immunogenicity for types 1 and 3 compared with tOPV [40].

An optimal immune response to bOPV requires multiple doses. Trials in Latin America and Bangladesh have demonstrated seroconversion rates of >94 percent to both type 1 and type 3 OPV among infants vaccinated with three bOPV doses at 6, 10, and 14 weeks of age [41,42].

Monovalent OPV vaccines and nOPV2 — Monovalent OPV vaccines for types 1, 2, and 3 (mOPV1, mOPV2, and mOPV3, respectively) are stockpiled by the Global Polio Eradication Initiative and deployed selectively in response to polio outbreaks [10].

A novel genetically stable type 2 OPV vaccine (nOPV2) has been created to address the ongoing risk of reversion of mOPV2 viruses to a virulent phenotype when deployed in response to cVDPV2 outbreaks. Clinical nOPV2 trials confirmed seroprotection and safety profiles comparable to mOPV2 [11,12,43]. Based on these studies, in 2020 the WHO authorized the emergency use of nOPV2 in all ages, including infants. Since then, 800 million doses have been administered in 23 countries [9,44]. (See "Global poliomyelitis eradication".)

Efficacy — The efficacy of OPV was never tested under conditions of exposure to natural polioviruses in the United States; however, nearly four decades of use from 1961 to 2000 provided overwhelming evidence of OPV effectiveness. OPV efficacy was directly evaluated during a type 1 poliovirus outbreak in Taiwan in the early 1980s when vaccine efficacy was estimated to be 82, 96, and 98 percent for one, two, and three or more doses, respectively [45].

Adverse effects — OPV viruses are shed from the oropharynx for up to 7 to 14 days after administration and in the stool for as long as 6 to 8 weeks in normal infants [46]. Stool shedding is accompanied by rapid loss of attenuating mutations in each of the three serotypes and an increase in phenotypic neurovirulence markers [47].

VAPP is a rare but important consequence of reversion to neurovirulence, which was reported in an average of nine persons per year in the United States between 1961 and 1997 [48,49] and which was estimated to occur in 3.8 persons per million births or 399 cases (range 306 to 490) in tOPV-using countries [50]. The removal of OPV2 from the vaccine in 2016 is has since reduced the incidence by approximately 60 percent. VAPP occurs in OPV recipients (mostly infants) and in direct contacts of OPV recipients (mostly adult caretakers with inadequate immunity). The overall risk is about 1 case per 900,000 first-dose OPV recipients [51]. Subsequent doses are less likely to be associated with VAPP in the United States but carry a higher risk in resource-poor countries, where OPV viruses may be less likely to replicate in the gastrointestinal tract following the first OPV dose [50]. Individuals with B cell immunodeficiency carry the highest risk, with an estimated VAPP rate of 2 per 1000 vaccinees [52,53]. For this reason, OPV is contraindicated for immunodeficient individuals.

In settings with inadequate vaccine coverage, OPV viruses can spread into the community as cVDPV that accumulate neurovirulent traits indistinguishable from wild type polioviruses through loss of attenuating mutations created in OPV. The emergence of cVDPV has fundamentally influenced plans for the eventual cessation of poliovirus immunization following eradication of poliomyelitis, which will include a strategy to discontinue OPV use, introduce IPV for risk mitigation, develop monovalent OPV vaccine stockpiles to deploy for cVDPV outbreaks like those occurring in Africa [2], and plan for containment of laboratory stocks of naturally occurring and attenuated polioviruses [54-56]. (See "Global poliomyelitis eradication".)

Other than VAPP, there are no adverse reactions attributed to OPV. The available data suggest that OPV does not increase the risk of fetal malformation or other adverse pregnancy outcomes [57].

RECOMMENDATIONS OF THE WHO — Most countries that adopt the World Health Organization (WHO) Expanded Program on Immunization (EPI) schedule for routine infant immunization administer bivalent oral poliovirus vaccine at birth and at 6, 10, and 14 weeks of age and two doses of inactivated poliovirus vaccine (IPV) at ≥14 weeks and 9 months of age to boost immunity to poliovirus types 1 and 3 and to provide protection against poliovirus type 2 [58]. This regimen induces seroconversion to all three types in >90 percent of infants by 12 months of age [59-61].

For countries that employ IPV alone, the WHO recommends three doses for countries that use a 2, 4, and 6 month schedule for routine infant immunization and four doses for countries that use a 6, 10, 14 week schedule; the fourth dose should be administered ≥6 months after the third dose.

For countries that have introduced sequential IPV-oral poliovirus vaccine (OPV) schedules, one or two IPV doses followed by a minimum of two OPV doses are recommended.

RECOMMENDATIONS OF THE CDC — Inactivated poliovirus vaccine (IPV) is the only vaccine recommended by the United States Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices and the American Academy of Pediatrics for routine immunization in the United States [62-64]. Oral poliovirus vaccine (OPV) is no longer licensed in the United States. Licensed vaccines containing IPV are summarized in the table (table 1).

Infants and children — The recommended polio vaccination series in the United States consists of four doses of IPV administered subcutaneously or intramuscularly [63]. The first and second doses are administered at 2 and 4 months of age, respectively. The third dose may be given at 6 to 18 months of age, and a fourth dose is given at 4 to 6 years of age before school entry [64]. The minimum interval between doses 1 and 2 and between doses 2 and 3 is four weeks, and the minimum interval between doses 3 and 4 is six months. The minimum age for dose 1 is six weeks. Minimum age and intervals should be applied when there is imminent threat of exposure, such as travel to an area in which polio is endemic or epidemic. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Children who are inadequately vaccinated should complete the vaccination series. The fourth dose is not required if the third dose of IPV was delayed until after the child's fourth birthday.

Adults — Polio vaccination is recommended for all adults known or suspected to be unvaccinated or incompletely vaccinated against polio [65].

In addition, polio vaccination is recommended for individuals at increased risk for exposure; this includes [66]:

●Travelers to areas or countries when polio is endemic or epidemic (see "Immunizations for travel", section on 'Poliovirus vaccine')

●Members of communities or population groups with disease caused by wild polioviruses

●Unvaccinated adults whose children will receive OPV

●Health care workers who have close contact with patients who might be excreting wild polioviruses or laboratory workers who handle specimens that may contain polioviruses

Adults at increased risk who have had a primary vaccination series with IPV or OPV should receive a single booster dose of IPV. Available data do not indicate the need for more than a single lifetime booster dose of IPV. An exception are adults who will be in a polio-exporting or polio-infected country for >4 weeks and received a booster dose >12 months earlier; they should receive an additional dose of IPV or OPV before exiting that country [67]. (See 'Recommendations for travelers' below.)

Adults at increased risk who are unvaccinated or whose vaccination status is not documented should receive a primary vaccination series with IPV. This consists of two doses of IPV at 4- to 8-week intervals and a third dose 6 to 12 months after the second dose. If this regimen cannot be completed within the recommended intervals before protection is needed, the following alternatives are recommended:

●If there are more than eight weeks before protection is needed, three doses of IPV should be given at least four weeks apart.

●If there are only four to eight weeks before protection is needed, two doses of IPV should be given at least four weeks apart.

●If there are less than four weeks before protection is needed, a single dose of IPV should be given.

For the second and third options, the remaining doses should be given later at the recommended intervals if the person remains at risk for exposure to poliovirus.

Pregnant women — Although adverse effects of IPV have not been documented in either the mother or the fetus, vaccination is not recommended during pregnancy on theoretical grounds [64,66]. If, however, a pregnant woman is at increased risk for infection and requires immediate protection, IPV should be given according to the above schedule in adults. (See "Immunizations during pregnancy", section on 'Poliovirus'.)

Immunocompromised patients — IPV is the only vaccine recommended for immunodeficient individuals and their household contacts [68]. However, a protective immune response cannot be assured in patients who are immunodeficient at the time of vaccination. The response in hematopoietic cell transplant recipients is optimized when more than one dose is administered at least 12 months after transplantation [69-71]. (See "Immunizations in hematopoietic cell transplant candidates and recipients" and "Immunizations in persons with HIV", section on 'Poliovirus vaccine'.)

Recommendations for travelers — The CDC recommends that travelers to poliovirus-affected areas be fully vaccinated against poliovirus with the age-appropriate vaccine series; adults should also receive a one-time booster dose of a poliovirus vaccine [72,73]. Information about recent cases can be found at the Global Polio Eradication Initiative website. Detailed recommendations regarding vaccination can be found at the CDC website.

In 2014, the international spread of wild poliovirus was declared by the World Health Organization to be a Public Health Emergency of International Concern. Temporary recommendations to reduce the international spread of wild poliovirus were issued, and the situation has been reassessed at three-month intervals thereafter. The country-specific temporary recommendations issued in August 2023 are available from the International Health Regulations Emergency committee [74,75].

The burden for implementation and enforcement of these recommendations lies with the poliovirus-affected countries. For countries that implement this recommendation, previous vaccination history is to be disregarded, and the required dose must have been given within the previous 12 months. Travel health practitioners should be aware of these individual country exit requirements in order to discuss whether vaccination prior to travel to the listed countries might be advisable. Travelers who are vaccinated should be provided with an International Certificate of Vaccination or Prophylaxis to serve as proof of vaccination.

Poliovirus immunization for travel is discussed in greater detail separately. (See "Immunizations for travel", section on 'Poliovirus vaccine'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in children and adolescents" and "Society guideline links: Immunizations in adults" and "Society guideline links: Polio".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Poliomyelitis (The Basics)")

●Beyond the Basics topics (see "Patient education: Why does my child need vaccines? (Beyond the Basics)" and "Patient education: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)")

SUMMARY

●Vaccine schedule – Inactivated poliovirus vaccine (IPV) is the preferred vaccine for developed countries because it does not cause vaccine-associated paralytic poliomyelitis (VAPP) and can be combined with other routine childhood vaccines. The polio vaccination series in the United States consists of four doses of IPV administered at 2 months, 4 months, 6 to 18 months, and 4 to 6 years of age. (See 'Inactivated poliovirus vaccine' above.)

●Preferred vaccine formulation – Bivalent oral poliovirus vaccine (bOPV) is the preferred vaccine for routine infant immunization in countries at increased risk of poliovirus transmission. Advantages to the use of bOPV include cost, ease of administration, and low risk of transmission of vaccine virus to unimmunized contacts. The WHO recommends a bivalent OPV dose at birth, followed by a primary series of three OPV doses (at 6, 10, and 14 weeks) as well as two IPV doses (at ≥14 weeks and 9 months of age). (See 'Live attenuated oral poliovirus vaccine' above.)

●Vaccine-derived polioviruses (VDPVs) – VDPVs are Sabin (OPV) virus derivatives that circulate in settings of low population immunity (eg, with low immunization rates) and revert to neurovirulence with ongoing transmission. The emergence of VDPV requires that use of all OPV vaccines must cease to achieve the goal of global poliomyelitis eradication. (See 'Adverse effects' above.)

●Vaccine-associated paralytic poliomyelitis (VAPP) – VAPP occurs as a result of reversion of an attenuated viral strain to a neurovirulent strain. OPV has been associated with rare cases of VAPP in vaccine recipients and their contacts. (See 'Adverse effects' above.)