Two-Year Duration of Immunity of Inactivated Poliovirus Vaccine: A Follow-up Study in Pakistan in 2020.

This was a follow-up study conducted in 2020 assessing changes in levels of type 2 poliovirus-neutralizing antibodies 2 years postimmunization in children who received inactivated poliovirus vaccine (IPV) in Karachi, Pakistan. Unexpectedly, the findings revealed an increase in seroprevalence of type 2 antibodies from 73.1% to 81.6% 1 year and 2 years after IPV, respectively. The increase in type 2 immunity could result from the intensive transmission of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Karachi during the second year of IPV administration. This study suggests that the cVDPV2 outbreak detected in Pakistan infected large proportions of children in Karachi. Clinical Trials Registration . NCT03286803.

Impact of Supplementary Immunization Activities using Novel Oral Polio Vaccine Type 2 during a Large outbreak of Circulating Vaccine-Derived Poliovirus in Nigeria.

BACKGROUND: Novel oral poliovirus vaccine (OPV) type 2 (nOPV2) has been made available for outbreak response under an emergency use listing authorization based on supportive clinical trial data. Since 2021 more than 350 million doses of nOPV2 were used for control of a large outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Nigeria. METHODS: Using a bayesian time-series susceptible-infectious-recovered model, we evaluate the field effectiveness of nOPV2 immunization campaigns in Nigeria compared with campaigns using monovalent OPV type 2 (mOPV2). RESULTS: We found that both nOPV2 and mOPV2 campaigns were highly effective in reducing transmission of cVDPV2, on average reducing the susceptible population by 42% (95% confidence interval, 28-54%) and 38% (20-51%) per campaign, respectively, which were indistinguishable from each other in this analysis (relative effect, 1.1 [.7-1.9]). Impact was found to vary across areas and between immunization campaigns. CONCLUSIONS: These results are consistent with the comparable individual immunogenicity of nOPV2 and mOPV2 found in clinical trials but also suggest that outbreak response campaigns may have small impacts in some areas requiring more campaigns than are suggested in current outbreak response procedures.

Monitoring the VDPV2 outbreak in Egypt during 2020-2021 highlights the crucial role of environmental surveillance and boosting immunization in combating Poliovirus.

BACKGROUND: Poliovirus is a highly infectious enterovirus (EV) that primarily affects children and can lead to lifelong paralysis or even death. Vaccine-derived polioviruses (VDPVs) are a great threat since they are derived from the attenuated virus in the Oral Poliovirus Vaccine (OPV) and can mutate to a more virulent form. The purpose of this study was to identify VDPV serotype 2 through the year 2020-2021 via surveillance of sewage samples collected from different localities and governorates in Egypt and stool specimens from Acute Flaccid Paralysis (AFP) cases. Both were collected through the national poliovirus surveillance system and according to the guidelines recommended by the WHO. METHODS: A total of 1266 sewage samples and 3241 stool samples from January 2020 to December 2021 were investigated in the lab according to World Health Organization (WHO) protocol for the presence of Polioviruses by cell culture, molecular identification of positive isolates on L20B cell line was carried out using real-time polymerase chain reactions (RT-PCR). Any positive isolates for Poliovirus type 2 and isolates suspected of Vaccine Derived Poliovirus Type 1 and type 3 screened by (VDPV1) or Vaccine Poliovirus Type 3 (VDPV3) assay in RT-PCR were referred for VP1 genetic sequencing. RESULTS: The outbreak was caused by circulating VDPV2 (cVDPV2) strains started in January 2021. By the end of February 2021, a total of 11 cVDPV2s were detected in sewage samples from six governorates confirming the outbreak situation. One additional cVDPV2 was detected later in the sewage sample from Qena (June 2021). The first and only re-emergence of VDPV2 in stool samples during the outbreak was in contact with Luxor in June 2021. By November 2021, a total of 80 VDPVs were detected. The Egyptian Ministry of Health and Population (MOHP), in collaboration with the WHO, responded quickly by launching two massive vaccination campaigns targeting children under the age of five. Additionally, surveillance systems were strengthened to detect new cases and prevent further spread of the virus. CONCLUSION: The continued threat of poliovirus and VDPVs requires ongoing efforts to prevent their emergence and spread. Strategies such as improving immunization coverage, using genetically stable vaccines, and establishing surveillance systems are critical to achieving global eradication of poliovirus and efficient monitoring of VDPVs outbreaks.

Worst-case scenarios: Modeling uncontrolled type 2 polio transmission.

In May 2016, the Global Polio Eradication Initiative (GPEI) coordinated the cessation of all use of type 2 oral poliovirus vaccine (OPV2), except for emergency outbreak response. Since then, paralytic polio cases caused by type 2 vaccine-derived polioviruses now exceed 3,000 cases reported by 39 countries. In 2022 (as of April 25, 2023), 20 countries reported detection of cases and nine other countries reported environmental surveillance detection, but no reported cases. Recent development of a genetically modified novel type 2 OPV (nOPV2) may help curb the generation of neurovirulent vaccine-derived strains; its use since 2021 under Emergency Use Listing is limited to outbreak response activities. Prior modeling studies showed that the expected trajectory for global type 2 viruses does not appear headed toward eradication, even with the best possible properties of nOPV2 assuming current outbreak response performance. Continued persistence of type 2 poliovirus transmission exposes the world to the risks of potentially high-consequence events such as the importation of virus into high-transmission areas of India or Bangladesh. Building on prior polio endgame modeling and assuming current national and GPEI outbreak response performance, we show no probability of successfully eradicating type 2 polioviruses in the near term regardless of vaccine choice. We also demonstrate the possible worst-case scenarios could result in rapid expansion of paralytic cases and preclude the goal of permanently ending all cases of poliomyelitis in the foreseeable future. Avoiding such catastrophic scenarios will depend on the development of strategies that raise population immunity to type 2 polioviruses.

Coordinated global cessation of oral poliovirus vaccine use: Options and potential consequences.

Due to the very low, but nonzero, paralysis risks associated with the use of oral poliovirus vaccine (OPV), eradicating poliomyelitis requires ending all OPV use globally. The Global Polio Eradication Initiative (GPEI) coordinated cessation of Sabin type 2 OPV (OPV2 cessation) in 2016, except for emergency outbreak response. However, as of early 2023, plans for cessation of bivalent OPV (bOPV, containing types 1 and 3 OPV) remain undefined, and OPV2 use for outbreak response continues due to ongoing transmission of type 2 polioviruses and reported type 2 cases. Recent development and use of a genetically stabilized novel type 2 OPV (nOPV2) leads to additional potential vaccine options and increasing complexity in strategies for the polio endgame. Prior applications of integrated global risk, economic, and poliovirus transmission modeling consistent with GPEI strategic plans that preceded OPV2 cessation explored OPV cessation dynamics and the evaluation of options to support globally coordinated risk management efforts. The 2022-2026 GPEI strategic plan highlighted the need for early bOPV cessation planning. We review the published modeling and explore bOPV cessation immunization options as of 2022, assuming that the GPEI partners will not support restart of the use of any OPV type in routine immunization after a globally coordinated cessation of such use. We model the potential consequences of globally coordinating bOPV cessation in 2027, as anticipated in the 2022-2026 GPEI strategic plan. We do not find any options for bOPV cessation likely to succeed without a strategy of bOPV intensification to increase population immunity prior to cessation.

Observational analysis of the immunogenicity and safety of various types of spinal muscular atrophy vaccines.

BACKGROUND: This study aimed to evaluate the immunogenicity and safety of different types of poliovirus vaccines. METHODS: A randomized, blinded, single-center, parallel-controlled design was employed, and 360 infants aged ≥ 2 months were selected as study subjects. They were randomly assigned to bOPV group (oral Sabin vaccine) and sIPV group (Sabin strain inactivated polio vaccine), with 180 infants in each group. Adverse reaction events in the vaccinated subjects were recorded. The micro-neutralization test using cell culture was conducted to determine the geometric mean titer (GMT) of neutralizing antibodies against poliovirus types I, II, and III in different groups, and the seroconversion rates were calculated. RESULTS: Both groups exhibited a 100% seropositivity rate after booster immunization. The titers of neutralizing antibodies for the three types were predominantly distributed within the range of 1:128 to 1:512. The fold increase of type I antibodies differed markedly between the two groups (P < 0.05). Moreover, the fold increase of type II and type III antibodies for poliovirus differed slightly between the two groups (P > 0.05). The fourfold increase rate in sIPV group was drastically superior to that in bOPV group (P < 0.05). When comparing the post-immunization GMT levels of type I antibodies in individuals who completed the full course of spinal muscular atrophy vaccination, bOPV group showed greatly inferior levels to sIPV group (P < 0.05). For type II and type III antibodies, individuals in bOPV group demonstrated drastically superior post-immunization GMT levels to those in sIPV group (P < 0.05). The incidence of adverse reactions between the bOPV and sIPV groups differed slightly (P > 0.05). CONCLUSION: These findings indicated that both the oral vaccine and inactivated vaccine had good safety and immunogenicity in infants aged ≥ 2 months. The sIPV group generated higher levels of neutralizing antibodies in serum, particularly evident in the post-immunization GMT levels for types II and III.

HLA-DQ-conferred risk for type 1 diabetes does not alter neutralizing antibody response to a widely used enterovirus vaccine, the poliovirus vaccine.

This study investigated whether children with HLA-DQ-conferred risk for type 1 diabetes (T1D) have an altered immune response to the widely-used enterovirus vaccine, namely poliovirus vaccine, and whether initiation of autoimmunity to pancreatic islets modulates this response. Neutralizing antibodies induced by the inactivated poliovirus vaccine against poliovirus type 1 (Salk) were analysed as a marker of protective immunity at the age of 18 months in a prospective birth cohort. No differences were observed in antibody titers between children with and without genetic risk for T1D (odds ratio [OR] = 0.90 [0.83, 1.06], p = 0.30). In the presence of the genetic risk, no difference was observed between children with and without islet autoimmunity (OR = 1.00 [0.78, 1.28], p = 1.00). This did not change when only children with the autoimmunity before 18 months of age were included in the analyses (OR = 1.00 [0.85, 1.18], p = 1.00). No effect was observed when groups were stratified based on autoantigen specificity of the first-appearing autoantibody (IAA or GADA). The children in each comparison group were matched for sex, calendar year and month of birth, and municipality. Accordingly, we found no indication that children who are at risk to develop islet autoimmunity would have a compromised humoral immune response which could have increased their susceptibility for enterovirus infections. In addition, the proper immune response supports the idea of testing novel enterovirus vaccines for the prevention of T1D among these individuals.

Dose-sparing effect of Sabin-derived inactivated polio vaccine produced in Japan by intradermal injection device for rats.

The live-attenuated oral polio vaccine has long been used as the standard for polio prevention, but in order to minimize the emergence of pathogenic revertants, the inactivated polio vaccine (IPV), which is administered intramuscularly or subcutaneously, is being increasingly demanded worldwide. However, there is a global shortage of IPV, and its cost is an obstacle in developing countries. Therefore, dose-sparing with intradermal administration of IPV has been investigated. In this study, rats were immunized by intradermal (ID) and intramuscular (IM) administration of Sabin-derived inactivated polio vaccine (sIPV) produced in Japan, and the immune responses were evaluated. The results showed that one-fifth (1/5)-dose of ID administration yielded neutralizing antibody titers comparable to the full-dose IM administration, whereas 1/5-dose of IM administration was less effective than the full dose. Furthermore, a vertical puncture-type ID injection device (Immucise) that was originally developed for humans was modified for rats, resulting in successful and stable ID administration into the thin skin of rats. Based on these results, the ID administration of sIPV using Immucise in clinical use is expected to offer benefits such as reduced amounts of vaccine per dose, cost-effectiveness, and thereby the feasibility of vaccination for more people.

Modeling scenarios for ending poliovirus transmission in Pakistan and Afghanistan.

Pakistan and Afghanistan pose risks for international transmission of polioviruses as the last global reservoir for wild poliovirus type 1 (WPV1) and a reservoir for type 2 circulating vaccine-derived polioviruses (cVDPV2s). Widespread transmission of WPV1 and cVDPV2 in 2019-2020 and resumption of intensive supplemental immunization activities (SIAs) in 2020-2021 using oral poliovirus vaccine (OPV) led to decreased transmission of WPV1 and cVDPV2 as of the end of 2021. Using an established dynamic disease transmission model, we explore multiple bounding scenarios with varying intensities of SIAs using bivalent OPV (bOPV) and/or trivalent tOPV (tOPV) to characterize potential die out of transmission. This analysis demonstrates potential sets of actions that may lead to elimination of poliovirus transmission in Pakistan and/or Afghanistan. Some modeled scenarios suggest that Pakistan and Afghanistan could increase population immunity to levels high enough to eliminate transmission, and if maintained, achieve WPV1 and cVDPV2 elimination as early as 2022. This requires intensive and proactive OPV SIAs to prevent transmission, instead of surveillance followed by reactive outbreak response. The reduction of cases observed in 2021 may lead to a false sense of security that polio has already or soon will die out on its own, but relaxation of immunization activities runs the risk of lowering population immunity to, or below, the minimum die-out threshold such that transmission continues. Transmission modeling may play a key role in managing expectations and supporting future modeling about the confidence of no virus circulation in anticipation of global certification decisions.

Regulations for the Manufacture and Control of Live Poliovirus Vaccine: International Experience and China's Path.

The eradication of poliomyelitis is a landmark achievement in the history of public health, providing strong protection for children's health. The introduction of the Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine is a prerequisite and safeguard for the large-scale production and use of domestically produced live poliovirus vaccines, serving as an indispensable component of vaccine safety. This article, based on archival documents, letters, collections of essays, and oral interviews, examines the historical experience of the development of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine. It contends that the emphasis on localization and the active engagement in international cooperation are critical factors in the swift introduction of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine.

Randomized Controlled Clinical Trial of Bivalent Oral Poliovirus Vaccine and Inactivated Poliovirus Vaccine in Nigerian Children.

BACKGROUND: We conducted a trial in Nigeria to assess the immunogenicity of the new bivalent oral poliovirus vaccine + inactivated poliovirus vaccine (bOPV+IPV) immunization schedule and gains in type 2 immunity with addition of second dose of IPV. The trial was conducted in August 2016-March 2017, well past the trivalent OPV-bOPV switch in April 2016. METHODS: This was an open-label, 2-arm, noninferiority, multicenter, randomized, controlled trial. We enrolled 572 infants aged ≤14 days and randomized them into 2 arms. Arm A received bOPV at birth, 6, and 10 weeks, bOPV+IPV at week 14, and IPV at week 18. Arm B received IPV each at 6, 10, and 14 weeks and bOPV at 18 weeks of age. RESULTS: Seroconversion rates for poliovirus types 1 and 3, respectively, were 98.9% (95% confidence interval [CI], 96.7-99.8) and 98.1% (95% CI, 88.2-94.8) in Arm A and 89.6% (95% CI, 85.4-93.0) and 98.5% (95% CI, 96.3-99.6) in Arm B. Type 2 seroconversion with 1 dose IPV in Arm A was 72.0% (95% CI, 66.2-77.3), which increased significantly with addition of second dose to 95.9% (95% CI, 92.8-97.9). CONCLUSIONS: This first trial on the new Expanded Program on Immunization (EPI) schedule in a sub-Saharan African country demonstrated excellent immunogenicity against poliovirus types 1 and 3 and substantial/enhanced immunogenicity against poliovirus type 2 after 1 to 2 doses of IPV, respectively.

Conserved Antigenic Structure of Contemporary Wild Poliovirus Type 1 Strains Endemic in Pakistan.

BACKGROUND: Elimination of poliovirus in Pakistan and Afghanistan is challenged by notions against the role of oral poliovirus vaccine (OPV) in eradicating contemporary wild poliovirus (WPV) strains. METHODS: A total of 1055 WPV type 1 (WPV1) strains isolated between 2013 and 2018 were categorized into 68 antigenic groups and tested for neutralization by OPV-derived antibodies. Molecular docking was conducted to determine neutralization efficiency of antibodies against WPV. The clinical significance of WPV1 variants was assessed to ascertain their role in patient outcomes. RESULTS: We found that 88% of WPV1 strains isolated from paralytic children belonged to a single antigenic lineage identical to the WPV1 strain detected in 1993. WPV1 antigenic variants were effectively neutralized by OPV-derived antibodies, with geometric mean titers comparable to the neutralization titers found for 3 strains in OPV (OPV1-3, 7.96-9.149 [95% confidence interval, 6.864-10.171]; WPV1 strains, 7.542-8.786 [6.493-9.869]). Docking examination underscored a strong antigen-antibody interaction despite variations within the viral protein 1 epitopes. There was no significant association (P = .78) with clinical prognosis among patients infected with antigenically diverse WPV1 strains and patient outcomes, including death. CONCLUSIONS: Our findings substantiate the robustness of OPV for neutralizing the contemporary WPV1 strains endemic in Pakistan and Afghanistan. Vaccination coverage must be augmented to achieve early eradication.

One Full or Two Fractional Doses of Inactivated Poliovirus Vaccine for Catch-up Vaccination in Older Infants: A Randomized Clinical Trial in Bangladesh.

BACKGROUND: The polio eradication endgame called for the removal of trivalent oral poliovirus vaccine (OPV) and introduction of bivalent (types 1 and 3) OPV and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies. METHODS: We conducted an open-label randomized clinical trial assessing 2 interventions, full or fractional-dose IPV (fIPV, one-fifth of IPV), administered at age 9-13 months with a second dose given 2 months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment. RESULTS: A single fIPV dose at age 9-13 months yielded 75% (95% confidence interval [CI], 6%-82%) seroconversion against type 2, whereas 2 fIPV doses resulted in 100% seroconversion compared with 94% (95% CI, 89%-97%) after a single full dose (P < .001). Two doses of IPV resulted in 100% seroconversion. CONCLUSIONS: Our study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either 1 full dose of IPV or 2 doses of fIPV could be used to vaccinate missed cohorts, 2 fIPV doses being antigen sparing and more immunogenic. CLINICAL TRIAL REGISTRATION: NCT03890497.

Safety and Immunogenicity of a New Inactivated Polio Vaccine Made From Sabin Strains: A Randomized, Double-Blind, Active-Controlled, Phase 2/3 Seamless Study.

BACKGROUND: A new inactivated polio vaccine made from Sabin strains (sIPV) was developed as part of the global polio eradication initiative. METHODS: This randomized, double-blind, active-controlled, phase 2/3 seamless study was conducted in 2 stages. Healthy infants aged 6 weeks were randomly assigned to receive 3 doses of 1 of 4 study vaccines at 6, 10, and 14 weeks of age (336 received low-, middle-, or high-dose sIPV, or conventional IPV [cIPV] in stage I, and 1086 received lot A, B, or C of the selected sIPV dose, or cIPV in stage II). The primary outcome was the seroconversion rate 4 weeks after the third vaccination. RESULTS: In stage I, low-dose sIPV was selected as the optimal dose. In stage II, consistency among the 3 manufacturing lots of sIPV was demonstrated. The seroconversion rates for Sabin and wild strains of the 3 serotypes after the 3-dose primary series were 95.8% to 99.2% in the lot-combined sIPV group and 94.8% to 100% in the cIPV group, proving the noninferiority of sIPV compared to cIPV. No notable safety risks associated with sIPV were observed. CONCLUSIONS: Low-dose sIPV administered as a 3-dose vaccination was safe and immunogenic compared to cIPV. CLINICAL TRIALS REGISTRATION: NCT03169725.

Immunogenicity of Reduced-Dose Monovalent Type 2 Oral Poliovirus Vaccine in Mocuba, Mozambique.

BACKGROUND: The monovalent type 2 oral poliovirus vaccine (mOPV2) stockpile is low. One potential strategy to stretch the existing mOPV2 supply is to administer a reduced dose: 1 drop instead of 2. METHODS: We conducted a randomized, controlled, open-label, noninferiority trial (10% margin) to compared immunogenicity after administration of 1 versus 2 drops of mOPV2. We enrolled 9-22-month-old infants from Mocuba district of Mozambique. Poliovirus neutralizing antibodies were measured in serum samples collected before and 1 month after mOPV2 administration. Immune response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) after vaccination or boosting titers by ≥4-fold for those with titers between 1:8 and 1:362 at baseline. The trial was registered at anzctr.org.au (no. ACTRN12619000184178p). RESULTS: We enrolled 378 children, and 262 (69%) completed per-protocol requirements. The immune response of mOPV2 was 53.6% (95% confidence interval, 44.9%-62.1%) and 60.6% (52.2%-68.4%) in 1-drop and 2-drop recipients, respectively. The noninferiority margin of the 10% was not reached (difference, 7.0%; 95% confidence interval, -5.0% to 19.0%). CONCLUSION: A small loss of immunogenicity of reduced mOPV2 was observed. Although the noninferiority target was not achieved, the Strategic Advisory Group of Experts on Immunization recommended the 1-drop strategy as a dose-sparing measure if mOPV2 supplies deteriorate further.

Economic assessment of incorporating the hexavalent vaccine as part of the National Immunization Program of Peru.

BACKGROUND: This study aimed to estimate the economic impact of replacing the current Peruvian primary immunization scheme for infants under 1 year old with an alternative scheme with similar efficacy, based on a hexavalent vaccine. METHODS: A cost-minimization analysis compared the costs associated with vaccine administration, adverse reactions medical treatment, logistical activities, and indirect social costs associated with time spent by parents in both schemes. A budgetary impact analysis assessed the financial impact of the alternative scheme on healthcare budget. RESULTS: Incorporating the hexavalent vaccine would result in a 15.5% net increase in healthcare budget expenditure ($48,281,706 vs $55,744,653). Vaccination costs would increase by 54.1%, whereas logistical and adverse reaction costs would be reduced by 59.8% and 33.1%, respectively. When including indirect social costs in the analysis, the budgetary impact was reduced to 8.7%. Furthermore, the alternative scheme would enable the liberation of 17.5% of national vaccines storage capacity. CONCLUSIONS: Despite of the significant reduction of logistical and adverse reaction costs, including the hexavalent vaccine into the National Immunization Program of Peru in place of the current vaccination scheme for infants under 1 year of age would increase the public financial budget of the government as it would represent larger vaccine acquisition costs. Incorporating the indirect costs would reduce the budgetary impact demonstrating the social value of the alternative scheme. This merits consideration by government bodies, and future studies investigating such benefits would be informative.

Immunization Against Poliomyelitis and the Challenges to Worldwide Poliomyelitis Eradication.

Both inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) have contributed to the rapid disappearance of paralytic poliomyelitis from developed countries despite possessing different vaccine properties. Due to cost, ease of use, and other properties, the Expanded Programme on Immunization added OPV to the routine infant immunization schedule for low-income countries in 1974, but variable vaccine uptake and impaired immune responses due to poor sanitation limited the impact. Following launch of the Global Polio Eradication Initiative in 1988, poliomyelitis incidence has been reduced by >99% and types 2 and 3 wild polioviruses are now eradicated, but progress against type 1 polioviruses which are now confined to Afghanistan and Pakistan has slowed due to insecurity, poor access, and other problems. A strategic, globally coordinated replacement of trivalent OPV with bivalent 1, 3 OPV in 2016 reduced the incidence of vaccine-associated paralytic poliomyelitis (VAPP) but allowed the escape of type 2 vaccine-derived polioviruses (VDPV2) in areas with low immunization rates and use of monovalent OPV2 in response seeded new VDPV2 outbreaks and reestablishment of type 2 endemicity. A novel, more genetically stable type 2 OPV vaccine is undergoing clinical evaluation and may soon be deployed prevent or reduce VDPV2 emergences.

A Randomized Phase 4 Study of Immunogenicity and Safety After Monovalent Oral Type 2 Sabin Poliovirus Vaccine Challenge in Children Vaccinated with Inactivated Poliovirus Vaccine in Lithuania.

BACKGROUND: Understanding immunogenicity and safety of monovalent type 2 oral poliovirus vaccine (mOPV2) in inactivated poliovirus vaccine (IPV)-immunized children is of major importance in informing global policy to control circulating vaccine-derived poliovirus outbreaks. METHODS: In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1-5-year-olds, we measured humoral and intestinal type 2 polio neutralizing antibodies before and 28 days after 1 or 2 mOPV2 doses given 28 days apart and measured stool viral shedding after each dose. Parents recorded solicited adverse events (AEs) for 7 days after each dose and unsolicited AEs for 6 weeks after vaccination. RESULTS: After 1 mOPV2 challenge, the type 2 seroprotection rate increased from 98% to 100%. Approximately 28 days after mOPV2 challenge 34 of 68 children (50%; 95% confidence interval, 38%-62%) were shedding virus; 9 of 37 (24%; 12%-41%) were shedding 28 days after a second challenge. Before challenge, type 2 intestinal immunity was undetectable in IPV-primed children, but 28 of 87 (32%) had intestinal neutralizing titers ≥32 after 1 mOPV2 dose. No vaccine-related serious or severe AEs were reported. CONCLUSIONS: High viral excretion after mOPV2 among exclusively IPV-vaccinated children was substantially lower after a subsequent dose, indicating induction of intestinal immunity against type 2 poliovirus.

Implication of a High Risk for Type 2 Vaccine-Derived Poliovirus Emergence and Transmission After the Switch From Trivalent to Bivalent Oral Poliovirus Vaccine.

BACKGROUND: China implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) and introduced 1 dose of inactivated poliovirus vaccine on 1 May 2016. We assessed the impact of the switch on the immunity level against poliovirus, especially type 2. METHODS: Children born between 2014 and 2017, who were brought to the hospitals in Urumqi city, Xinjiang Province in 2017, were enrolled and blood samples were collected to test for antibody titers against poliovirus. A comparison of seroprevalence between the children born before (preswitch group) and after the switch (postswitch group) was performed to assess the impact of the switch on the immunity level against polio. RESULTS: A total of 172 subjects were enrolled. The overall seroprevalences were 98.8%, 79.1%, and 98.3% for types 1, 2, and 3, respectively. Seroprevalence for type 2 significantly decreased from 91.6% in the preswitch group to 67.4% in the postswitch group, but no statistically significant change was observed for both types 1 and 3. CONCLUSIONS: The switch from tOPV to bOPV can provide high-level immunity against types 1 and 3 but not against type 2, indicating a high risk of type 2 vaccine-derived poliovirus emergence and transmission.

Coordinated Response to Imported Vaccine-Derived Poliovirus Infection, Barcelona, Spain, 2019-2020.

In 2019, the Public Health Agency of Barcelona, Spain, was notified of a vaccine-derived poliovirus infection. The patient had an underlying common variable immunodeficiency and no signs of acute flaccid paralysis. We describe the ongoing coordinated response to contain the infection, which included compassionate-use treatment with pocapavir.