Introduction Of Inactivated Poliovirus Vaccine Research Articles

Global oral poliovirus vaccine stockpile management as an essential preparedness and response mechanism for type 2 poliovirus outbreaks following global oral poliovirus vaccine type 2 withdrawal.

Following the global declaration of indigenous wild poliovirus type 2 eradication in 2015, the world switched to oral polio vaccine (OPV) that removed the type 2 component. This 'switch' included the widespread introduction of inactivated poliovirus vaccine and the creation of a stockpile of monovalent type 2 OPV (mOPV2) to respond to potential polio virus Type 2 (PV2) outbreaks and events. With subsequent detection of outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2), it was necessary to use this stockpile for outbreak response. Not only were more outbreaks detected than anticipated in the first few years after the switch, but the number of supplemental immunization activities (SIAs) used to stop transmission was often high, and in many cases did not stop wider transmission. Use of mOPV type 2 led in some locations to the emergence of new outbreaks that required further use of the vaccine from the stockpile. In the following years, stockpile management became a critical element of the cVDPV2 outbreak response strategy and continued to evolve to include trivalent OPV and genetically stabilized 'novel OPV type 2' vaccines in the stockpile. An overview of this process and its evolution is presented to highlight several of these management challenges. The unpredictable vaccine demand, fixed production and procurement timelines, resource requirements, and multiple vaccine types contributes to the complexity of assuring appropriate vaccine availability for this critical programmatic need to stop outbreaks.

Inactivated enterovirus A71 vaccines and moving forward.

The inactivated poliovirus vaccine (IPV) was introduced in 1955 in the USA for the first time globally, and the excellent efficacy and safety of IPV have been widely accepted worldwide. IPV effectively elicits serum neutralizing antibodies against poliovirus types 1, 2, and 3 by multiple IPV doses and effectively prevents paralytic poliomyelitis.[1] However, vaccines against non-polio enteroviruses (NPEVs) had not been licensed for almost 60 years since the introduction of IPV. In response to the large-scale outbreaks of hand, foot, and mouth disease (HFMD), including cases with severe and fatal neurological complications associated with enterovirus A71 (EV-A71), developing EV-A71 vaccine had been encouraged mainly in countries in the Western Pacific Region (WPR).[2,3] Three inactivated EV-A71 vaccines manufactured by three companies were approved in China from 2015 to 2016 to prevent EV-A71-associated diseases as the world's first NPEV vaccines.

Surveillance of adverse events following the introduction of inactivated poliovirus vaccine made from Sabin strains (sIPV) to the Chinese EPI and a comparison with adverse events following inactivated poliovirus vaccine made from wild strains (wIPV) in Jiangsu, China

ABSTRACT One dose of inactivated poliovirus vaccine (IPV) was introduced into the Chinese Expanded Program on Immunization (EPI) in 2016. IPV made from Sabin strains (sIPV) was newly licensed in China and its safety has been concerned. This study aimed to evaluate the safety of sIPV and provide a comparison with conventional IPV made from wild strains (wIPV). We collected all IPV-related AEFI reports in Jiangsu from the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) for 2016–2019. We obtained the administered doses of IPV from the Jiangsu provincial Electronic Immunization Registries System (JSEIRS). The AEFI reporting rates per 100,000 doses of vaccine administered were compared for sIPV and wIPV. A total of 699 sIPV and 908 wIPV AEFI cases were collected by CNAEFIS in Jiangsu during 2016–2019. The overall AEFI reporting rates were 53.02 per 100,000 doses and 41.25 per 100,000 doses for sIPV and wIPV, respectively (P < .001). For both sIPV and wIPV, the AEFIs were mainly classified as common adverse reactions. The reporting rate of common adverse reactions was higher for sIPV than for wIPV (P < .001). The most frequently reported symptoms/signs were fever, persistent crying, injection site erythema/swelling, rash, and injection site induration. Only 1.14% of sIPV-associated and 2.31% of wIPV-associated AEFI cases were diagnosed as serious. No difference in reporting rate was observed for serious AEFIs (P = .272). sIPV has a favorable safety profile, although it exhibits a slightly higher reporting rate of common adverse reactions than wIPV.

Immunogenicity of three sequential schedules with Sabin inactivated poliovirus vaccine and bivalent oral poliovirus vaccine in Zhejiang, China: an open-label, randomised, controlled trial

The globally synchronised introduction of inactivated poliovirus vaccine (IPV) and replacement of trivalent oral poliovirus vaccine (OPV) with bivalent OPV (bOPV) were successfully implemented in China's routine immunisation programme in May, 2016. In response to the global shortage of Salk-strain IPV, Sabin-strain IPV production was encouraged to develop and use in low-income and middle-income countries. We assessed the immunogenicity of the current routine poliovirus vaccination schedule in China and compared it with alternative schedules that use Sabin-strain IPV (sIPV) and bOPV. This open-label, randomised, controlled trial recruited healthy infants aged 60-75 days from two centres in Zhejiang, China. Eligible infants were full-term, due for their first polio vaccination, weighed more than 2·5 kg at birth, were healthy on physical examination with no obvious medical conditions, and had no contraindications to vaccination. Infants were randomly assigned (1:1:1) using permuted block randomisation (block size of 12) to one of three polio vaccination schedules, with the first, second, and third doses given at ages 2 months, 3 months, and 4 months, respectively: sIPV-bOPV-bOPV (1sIPV+2bOPV group; current regimen), sIPV-sIPV-bOPV (2sIPV+1bOPV group), or sIPV-sIPV-sIPV (3sIPV group). The primary endpoint was the proportion of infants with seroconversion to each of the three poliovirus serotypes 1 month after the third dose. Serious and medically important adverse events were monitored for up to 30 days after each vaccination. We assessed immunity in the per-protocol population (all children who completed all three vaccinations and had pre-vaccination and post-vaccination laboratory data) and safety in all children who received at least one dose of study vaccine. This trial is registered with Clinicaltrials.gov, NCT03147560. Between May 1, 2016, and Dec 1, 2017, we enrolled and randomly assigned 528 eligible infants to one of the three treatment groups (176 in each group); 473 infants (158 in the 1sIPV+2bOPV group, 152 in the 2sIPV+1bOPV group, and 163 in the 3sIPV group) were included in the per-protocol population. 100% seroconversion against poliovirus types 1 and 3 was observed in all three groups. Infants who received an immunisation schedule containing bOPV had significantly higher antibody titres against poliovirus types 1 and 3 than did the sIPV-only group (2048 in all three treatment groups; p<0·0001). Seroconversion against type 2 poliovirus was observed in 98 (62%) infants in the 1sIPV+2bOPV group, 145 (95%) infants in the 2sIPV+1bOPV group, and 161 (99%) infants in the 3sIPV group. No serious adverse events occurred during the study; 14 minor, transient adverse events were observed, with no significant differences across study groups. All three study schedules were well tolerated and highly immunogenic against poliovirus types 1 and 3. Schedules containing two or three sIPV doses had higher seroconversion rates against poliovirus type 2 than did the schedule with a single dose of sIPV. Our findings support inclusion of two sIPV doses in the routine poliovirus vaccination schedule in China to provide better protection against poliovirus type 2 than provided by the current regimen. Chinese Center for Disease Control and Prevention and China National Biotec Group Company.

Valuing the cost of improving Chilean primary vaccination: a cost minimization analysis of a hexavalent vaccine

BackgroundThe phased withdrawal of oral polio vaccine (OPV) and the introduction of inactivated poliovirus vaccine (IPV) is central to the polio ‘end-game’ strategy.MethodsWe analyzed the cost implications in Chile of a switch from the vaccination scheme consisting of a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV/OPV vaccines to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV (Hexaxim®) from a societal perspective. Cost data were collected from a variety of sources including national estimates and previous vaccine studies. All costs were expressed in 2017 prices (US$ 1.00 = $Ch 666.26).ResultsThe overall costs associated with the vaccination scheme (4 doses of pentavalent vaccine plus 1 dose IPV and 3 doses OPV) from a societal perspective was estimated to be US$ 12.70 million, of which US$ 8.84 million were associated with the management of adverse events related to wP. In comparison, the cost associated with the 4-dose scheme with a hexavalent vaccine (based upon the PAHO reference price) was US$ 19.76 million. The cost of switching to the hexavalent vaccine would be an additional US$ 6.45 million. Overall, depending on the scenario, the costs of switching to the hexavalent scheme would range from an additional US$ 2.62 million to US$ 6.45 million compared with the current vaccination scheme.ConclusionsThe switch to the hexavalent vaccine schedule in Chile would lead to additional acquisition costs, which would be partially offset by improved logistics, and a reduction in adverse events associated with the current vaccines.

Insights From Modeling Preventive Supplemental Immunization Activities as a Strategy to Eliminate Wild Poliovirus Transmission in Pakistan and Afghanistan.

Many countries use supplemental immunization activities (SIAs) with oral poliovirus vaccine (OPV) to keep their population immunity to transmission high using preventive, planned SIAs (pSIAs) and outbreaks response SIAs (oSIAs). Prior studies suggested that investment in pSIAs saved substantial health and financial costs due to avoided outbreaks. However, questions remain about the benefits of SIAs, particularly with the recent introduction of inactivated poliovirus vaccine (IPV) into routine immunization in all OPV-using countries. The mounting costs of polio eradication activities and the need to respond to oSIAs threatens the use of limited financial resources for pSIAs, including in the remaining countries with endemic transmission of serotype 1 wild poliovirus (WPV1) (i.e., Pakistan and Afghanistan). A recent updated global poliovirus transmission model suggested that the Global Polio Eradication Initiative (GPEI) is not on track to stop transmission of WPV1 in Pakistan and Afghanistan. We use the updated global model to explore the role of pSIAs to achieve WPV1 eradication. We find that unless Pakistan and Afghanistan manage to increase the quality of bivalent OPV (bOPV) pSIAs, which we model as intensity (i.e., sufficiently high-coverage bOPV pSIAs that reach missed children), the model does not lead to successful eradication of WPV1. Achieving WPV1 eradication, the global objectives of the GPEI, and a successful polio endgame depend on effective and sufficient use of OPV. IPV use plays a negligible role in stopping transmission in Pakistan and Afghanistan and most other countries supported by the GPEI, and more IPV use will not help to stop transmission.

Immunogenicity of Three Sequential Schedules with Sabin Inactivated Poliovirus Vaccine and Bivalent Oral Poliovirus Vaccine: An Open-Label, Randomized, Controlled Trail in Zhejiang, China

Background: The globally-synchronized introduction of inactivated poliovirus vaccine (IPV) and replacement of trivalent oral poliovirus vaccine (tOPV) with bivalent oral poliovirus vaccine (bOPV) was successfully implemented in China's routine immunization system in April and May of 2016. We assessed the immunogenicity of the current routine poliovirus vaccination schedule and compared it to alternative schedules that use Sabin-strain IPV (sIPV) and bOPV. Methods: We conducted an open-label, randomized, controlled trial among healthy infants in Zhejiang province, China. After obtaining informed consent, infants were randomly allocated to receive three polio vaccinations at age 2, 3 and 4 months in one of three sequential schedules: sIPV-bOPV-bOPV (Group 1), sIPV-sIPV-bOPV (Group 2), or sIPV-sIPV-sIPV (Group 3). We assessed immunogenicity in the three groups by measuring poliovirus type-specific antibody levels in sera immediately before the first dose and one month after the third dose. We assessed immunity in a per-protocol (PP) analysis (among subjects with no protocol deviations), and assessed safety in an intention-to-treat analysis (among subjects receiving at least one dose of study vaccine). Results: We enrolled and assigned 528 eligible infants to one of the three treatment groups (176 in each group); 473 infants (158 in Group 1, 152 in Group 2, and 163 in Group 3) completed the PP requirements. Three doses of sIPV or bOPV elicited seroconversion in 100% of subjects against poliovirus types 1 and 3 regardless of study group. Infants who received sIPV followed by bOPV had significantly higher antibody titers against poliovirus types 1 and 3 than did the sIPV-only group. Seroconversion against type 2 polio was observed in 62.03% of Group 1 infants, 95.39% of Group 2 infants, and 98.77% of Group 3 infants. The percentages of children with seroprotective antibody titers to poliovirus type 2 after vaccination were 63.29%, 96.05%, and 98.77% in Groups 1, 2, and 3. No serious adverse events occurred during the study; 14 minor, transient adverse events were observed with no significant differences across study groups. Conclusion: All three study schedules were well tolerated and highly immunogenic against poliovirus types 1 and 3. Schedules containing 2 or 3 sIPV doses had higher seroconversion rates against poliovirus type 2 than the schedule with a single dose of sIPV. Our findings support using a two-sIPV-dose routine poliovirus vaccination schedule in China to provide better protection against poliovirus type 2. Clinical Trial Number: The study is registered with ClinicalTrials.gov, number NCT03147560, and has been completed. Funding Statement: The study was funded by Chinese Center for Disease Control and Prevention (funds number: 131031001000150001) and China National Biotec Group Company (CNBG). Declaration of Interests: Yan Liu received grants from Zhejiang provincial basic public welfare research projects (LGF18H260002) and Hangzhou research projects for agricultural and social development (20180533B94). Ethics Approval Statement: The study protocol was approved by the ethics committee of Zhejiang Provincial Center for Disease Control and Prevention. Written informed consent was obtained from legal guardians of the subjects before enrollment.

Polio vaccination coverage and seroprevalence of poliovirus antibodies after the introduction of inactivated poliovirus vaccines for routine immunization in Japan

In Japan, the oral poliovirus vaccine (OPV) was changed to 2 types of inactivated poliovirus vaccine (IPV), the standalone conventional IPV (cIPV) and the Sabin-derived IPV combined with diphtheria-tetanus-acellular pertussis vaccine (DTaP-sIPV), for routine immunization in 2012. We evaluated polio vaccination coverage and the seroprevalence of poliovirus antibodies using data from the National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD) from 2011 to 2015. Several years before the introduction of IPV in 2012, OPV administration for children was refused by some parents because of concerns about the risk of vaccine-associated paralytic poliomyelitis. Consequently, in children aged <1 years who were surveyed in 2011–2012, polio vaccination coverage (45.0–48.8%) and seropositivity rates for poliovirus (type 1: 51.7–65.9%, type 2: 48.3–53.7%, and type 3: 15.0–29.3%) were decreased compared to those surveyed in 2009. However, after IPV introduction, the vaccination coverage (95.5–100%) and seropositivity rates (type 1: 93.2–96.6%, type 2: 93.1–100%, and type 3: 88.6–93.9%) increased among children aged <1 years in 2013–2015. In particular, seropositivity rates and geometric mean titers (GMTs) for poliovirus type 3 in <5-year-old children who received 4 doses of IPV (98.5% and 247.4, respectively) were significantly higher than in those who received 2 doses of OPV (72.5% and 22.9, respectively). Furthermore, in <5-year-old children who received 4 doses of either DTaP-sIPV or cIPV, the seropositivity rates and the GMTs for all 3 types of poliovirus were similarly high (96.5–100% and 170.3–368.8, respectively). Our findings from the NESVPD demonstrate that both the vaccination coverage and seropositivity rates for polio remained high in children after IPV introduction.

Introduction of inactivated poliovirus vaccine in the Philippines: Effect on health care provider and infant caregiver attitudes and practices

BackgroundThe introduction of inactivated poliovirus vaccine (IPV) to the Philippines’ national immunization schedule meant the addition of a third injectable vaccine at a child’s 14-week immunization visit. Although previous studies have shown that providing multiple vaccines at the same time affected neither the risk of severe adverse events nor vaccine efficacy, concerns were raised that providing three injections at a single visit, with two injections in one leg, might be unacceptable to health care providers (HCP) and infant caregivers. MethodsWe conducted pre- and post-IPV introduction surveys on the acceptance and acceptability of the additional injectable vaccine in three of the Philippines’ 17 administrative regions. Regions 3 and 6 were included in the pre-introduction phase and Regions 3, 6 and 10 were included in the post-introduction phase. Thirty public health centers (PHCs) were randomly sampled from each region. HCPs and infant caregivers were interviewed. In addition, vaccination records from a minimum of 20 eligible children pre-introduction and 10 children post-introduction per PHC were reviewed. Results and discussionWe interviewed 89 HCPs and 286 infant caregivers during the pre-introduction phase and 137 HCPs and 455 caregivers during the post-introduction phase. Among 986 vaccination records reviewed post-introduction, 84% (n = 826) of children received all three recommended injections at one visit, with a range from 61% (209/342) in Region 10 to 100% (328/328) in Region 3. The proportion of HCPs reporting that they had administered three or more injectable vaccines and the proportion of caregivers that would be comfortable with their child receiving three or more injectable vaccines at one visit increased from pre- to post-introduction (p < 0.0001 for both). Eighty-seven percent of HCPs that had administered three or more injectable vaccines post-introduction reported being comfortable or very comfortable with the number of vaccines they had administered.

Addressing the Challenges and Opportunities of the Polio Endgame: Lessons for the Future.

The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever.

Succeeding in New Vaccine Introduction: Lessons Learned From the Introduction of Inactivated Poliovirus Vaccine in Cameroon, Kenya, and Nigeria

Introducing a new vaccine is a large-scale endeavor that can face many challenges, resulting in introduction delays and inefficiencies. The development of national task teams and tools, such as prelaunch trackers, for the introduction of new vaccines (hereafter, “new vaccine introductions” [NVIs]) can help countries implement robust project management systems, front-load critical preparatory activities, and ensure continuous communication around vaccine supply and financing. In addition, implementing postlaunch assessments to take rapid corrective action accelerates the uptake of the new vaccines. NVIs can provide an opportunity to strengthen routine immunization, through strengthening program management systems or by reinforcing local immunization managers’ abilities, among others. This article highlights key lessons learned during the introduction of inactivated poliovirus vaccine in 3 countries that would make future NVIs more successful. The article concludes by considering how the Immunization Systems Management Group of the Global Polio Eradication Initiative has been useful to the NVI process and how such global structures could be further enhanced.

Comparison of IPV to tOPV week 39 boost of primary OPV vaccination in Indian infants: an open labelled randomized controlled trial.

BackgroundThe final endgame strategy of global polio eradication initiative includes switching from trivalent oral poliovirus vaccines (tOPV) to bivalent oral polio vaccine (bOPV), and introduction of inactivated poliovirus vaccine (IPV). This study compares IPV with tOPV week 39 boost in Indian infants.MethodsStarting 28 March 2012, we enrolled 372 Indian infant-mother pairs from Kolkata, India in an open-label, block-randomized, controlled trial comparing a 39 week tOPV to an IPV boost among infants immunized with three doses of tOPV. The primary outcome was mucosal immunity to poliovirus as measured by fecal polio virus shedding after OPV challenge. The secondary outcome was humoral response as defined by >1:8 titers for neutralizing antibodies at week 40. Seroconversion was measured by change in level of antibody titers from week 18 to week 40. The analyses were performed by both intention-to-treat (ITT) and per-protocol (PP) comparing the occurrences of outcomes between the arms of the study.FindingsBoth the study arms provided equivalent mucosal immunity at 52 weeks with a total shedding prevalence of 28%. Vaccination with IPV resulted in significantly higher seroconversion rates for Polio type 2 (p = 0.03) and Polio type 3 (p < 0.01).ConclusionsThis study indicates that an IPV boost at week 39 is equivalent to tOPV in intestinal immunity, and provides higher seroconversion compared to tOPV. The major limitation of the study was the additional OPV doses receive by infants during pulse polio immunization resulted in additional mucosal boosting, diminishing the impact of IPV or tOPV boost at week 39. However, IPV for OPV boost should prove to be a step forward in the global polio eradication initiative to reduce the problem of circulating vaccine-derived poliovirus (cVDPV).

Priming after Inactivated Poliovirus Vaccine: Implications for Polio Eradication

Progress toward polio eradication has shifted attention to developing and implementing the endgame strategies. The process of replacing oral poliovirus vaccine (OPV) with inactivated poliovirus vaccine (IPV) has begun, starting with the withdrawal of Sabin type 2 poliovirus from OPV in April 2016, and the simultaneous introduction of IPV in routine immunization schedules. The addition of a single dose of IPV to the bivalent type 1 and type 3 OPV (bOPV) schedule was recommended as a risk mitigation strategy to prevent paralytic disease due to poliovirus type 2. Single-dose IPV, however, is insufficient for inducing seroconversion in a majority of the vaccinees, despite immune priming ability. In this report we review studies that explore immune priming and memory conferred by single-dose IPV even in situations where seroconversion is not achieved, and discuss the current knowledge gaps and their implications for sustaining global polio eradication and for refining of the endgame strategies.

Coverage estimates and patterns of inactivated poliovirus vaccine (IPV) use prior to and during the polio eradication endgame, Jinan City, China, 2010–2015

ABSTRACTBackground: Use of inactivated poliovirus vaccine (IPV) in Jinan during the polio eradication endgame has not been previously documented. Two IPV-containing vaccines were made available as an option for Jinan parents in 2009. We describe coverage levels and patterns of use of IPV over time using data from the Jinan Childhood Immunization Information Management System (JNCIIMS).Methods: Children born between January 2010 and December 2014 who were registered in JNCIIMS were included in this study. Vaccination records were obtained from JNCIIMS on April 30, 2015. JNCIIMS distinguishes among available poliovirus vaccines; doses administered data were used to describe IPV usage over time. We identified the polio vaccination sequences used by children in the 2012 and 2013 birth cohorts. Coverage estimates were analyzed by birth cohort and migration status. We developed 3 categories for analysis: “resident child,” “migrant child” and “other child” according to migration status.Results: In total, 12,354 (11.7%) IPV, 5,893(5.6%) DTP-IPV-Hib vaccine and 87,054(82.7%) OPV doses were administered to children in the 2010 to 2014 birth cohorts. The proportion of children using an IPV-only schedule increased each year, consistent with the introduction of IPV that is called for by the Polio Eradication Endgame Strategic Plan 2013–2018. During this time, 4.7% children used a schedule containing both IPV and oral poliovirus vaccine (OPV). In the 2012 to 2013 birth cohorts, 14.4% children used an IPV-only schedule; 5.7% children used a sequential schedule, and 79.9% used OPV-only schedule. Use of IPV only schedules was higher among migrant children than among resident children. Among those sequential schedule using both IPV and OPV, 87.2% children used IPV for the first dose and 12.8% used OPV for the first dose.Conclusions: JNCIIMS provided a mechanism for tracking IPV and OPV vaccination patterns, and showed areas in need of improvement. Ensuring appropriately sequenced IPV and OPV supports reduction of risk of vaccine associated paralytic polio.

Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial

Replacement of the trivalent oral poliovirus vaccine (tOPV) with bivalent types 1 and 3 oral poliovirus vaccine (bOPV) and global introduction of inactivated poliovirus vaccine (IPV) are major steps in the polio endgame strategy. In this study, we assessed humoral and intestinal immunity in Latin American infants after three doses of bOPV combined with zero, one, or two doses of IPV. This open-label randomised controlled multicentre trial was part of a larger study. 6-week-old full-term infants due for their first polio vaccinations, who were healthy on physical examination, with no obvious medical conditions and no known chronic medical disorders, were enrolled from four investigational sites in Colombia, Dominican Republic, Guatemala, and Panama. The infants were randomly assigned by permuted block randomisation (through the use of a computer-generated list, block size 36) to nine groups, of which five will be discussed in this report. These five groups were randomly assigned 1:1:1:1 to four permutations of schedule: groups 1 and 2 (control groups) received bOPV at 6, 10, and 14 weeks; group 3 (also a control group, which did not count as a permutation) received tOPV at 6, 10, and 14 weeks; group 4 received bOPV plus one dose of IPV at 14 weeks; and group 5 received bOPV plus two doses of IPV at 14 and 36 weeks. Infants in all groups were challenged with monovalent type 2 vaccine (mOPV2) at 18 weeks (groups 1, 3, and 4) or 40 weeks (groups 2 and 5). The primary objective was to assess the superiority of bOPV-IPV schedules over bOPV alone, as assessed by the primary endpoints of humoral immunity (neutralising antibodies-ie, seroconversion) to all three serotypes and intestinal immunity (faecal viral shedding post-challenge) to serotype 2, analysed in the per-protocol population. Serious and medically important adverse events were monitored for up to 6 months after the study vaccination. This study is registered with ClinicalTrials.gov, number NCT01831050, and has been completed. Between May 20, 2013, and Aug 15, 2013, 940 eligible infants were enrolled and randomly assigned to the five treatment groups (210 to group 1, 210 to group 2, 100 to group 3, 210 to group 4, and 210 to group 5). One infant in group 1 was not vaccinated because their parents withdrew consent after enrolment and randomisation, so 939 infants actually received the vaccinations. Three doses of bOPV or tOPV elicited type 1 and 3 seroconversion rates of at least 97·7%. Type 2 seroconversion occurred in 19 of 198 infants (9·6%, 95% CI 6·2-14·5) in the bOPV-only groups, 86 of 88 (97·7%, 92·1-99·4) in the tOPV-only group (p<0·0001 vs bOPV-only), and 156 of 194 (80·4%, 74·3-85·4) infants in the bOPV-one dose of IPV group (p<0·0001 vs bOPV-only). A further 20 of 193 (10%) infants in the latter group seroconverted 1 week after mOPV2 challenge, resulting in around 98% of infants being seropositive against type 2. After a bOPV-two IPV schedule, all 193 infants (100%, 98·0-100; p<0·0001 vs bOPV-only) seroconverted to type 2. IPV induced small but significant decreases in a composite serotype 2 viral shedding index after mOPV2 challenge. 21 serious adverse events were reported in 20 patients during the study, including two that were judged to be possibly related to the vaccines. Most of the serious adverse events (18 [86%] of 21) and 24 (80%) of the 30 important medical events reported were infections and infestations. No deaths occurred during the study. bOPV provided humoral protection similar to tOPV against polio serotypes 1 and 3. After one or two IPV doses in addition to bOPV, 80% and 100% of infants seroconverted, respectively, and the vaccination induced a degree of intestinal immunity against type 2 poliovirus. Bill & Melinda Gates Foundation.

Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial

BackgroundThe Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain. MethodsBetween May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle. FindingsWe randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was −3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of −10% to +4%. Results for shedding analyses stratified by poliovirus type were similar. ConclusionsNeither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection.

Health and economic consequences of different options for timing the coordinated global cessation of the three oral poliovirus vaccine serotypes.

BackgroundWorld leaders remain committed to globally-coordinated oral poliovirus vaccine (OPV) cessation following successful eradication of wild polioviruses, but the best timing and strategy for implementation depend on existing and emerging conditions.MethodsUsing an existing integrated global poliovirus risk management model, we explore alternatives to the current timing plan of coordinated cessation of each OPV serotype (i.e., OPV1, OPV2, and OPV3 cessation for serotypes 1, 2, and 3, respectively). We assume the current timing plan involves OPV2 cessation in 2016 followed by OPV1 and OPV3 cessation in 2019 and we compare this to alternative timing options, including cessation of all three serotypes in 2018 or 2019, and cessation of both OPV2 and OPV3 in 2017 followed by OPV1 in 2019.ResultsIf Supplemtal Immunization Activity frequency remains sufficiently high through cessation of the last OPV serotype, then all OPV cessation timing options prevent circulating vaccine-derived poliovirus (cVDPV) outbreaks after OPV cessation of any serotype. The various OPV cessation timing options result in relatively modest differences in expected vaccine-associated paralytic poliomyelitis cases and expected total of approximately 10–13 billion polio vaccine doses used. However, the expected amounts of vaccine of different OPV formulations needed changes dramatically with each OPV cessation timing option. Overall health economic impacts remain limited for timing options that only change the OPV formulation but preserve the currently planned year for cessation of the last OPV serotype and the global introduction of inactivated poliovirus vaccine (IPV) introduction. Earlier cessation of the last OPV serotype or later global IPV introduction yield approximately $1 billion in incremental net benefits due to saved vaccination costs, although the logistics of implementation of OPV cessation remain uncertain and challenging.ConclusionsAll countries should maintain the highest possible levels of population immunity to transmission for each poliovirus serotype prior to the coordinated cessation of the OPV serotype to manage cVDPV risks. If OPV2 cessation gets delayed, then global health leaders should consider other OPV cessation timing options.

Good news for billions of children who will receive IPV

In The Lancet Infectious Diseases, Shahed Iqbal and colleagues 1 Iqbal S Shi J Seib K et al. Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12. Lancet Infect Dis. 2015; (published online Aug 17.)http://dx.doi.org/10.1016/S1473-3099(15)00059-6 Google Scholar present their analysis of data from the US Vaccine Adverse Event Reporting System (VAERS), the largest database of reported events temporally associated with, but not necessarily causally related to, the delivery of inactivated poliovirus vaccine (IPV). Their results show low numbers of temporally associated events reported with the delivery of more than 250 million IPV doses in the USA and no substantial adverse events, which confirms the safety of IPV. 1 Iqbal S Shi J Seib K et al. Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12. Lancet Infect Dis. 2015; (published online Aug 17.)http://dx.doi.org/10.1016/S1473-3099(15)00059-6 Google Scholar In view of the unprecedented global adoption of IPV as all countries prepare for the eradication of wild polioviruses and globally coordinated cessation of oral poliovirus vaccine (OPV), this news is positive. 1 Iqbal S Shi J Seib K et al. Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12. Lancet Infect Dis. 2015; (published online Aug 17.)http://dx.doi.org/10.1016/S1473-3099(15)00059-6 Google Scholar Although only 65 countries had included IPV in their routine immunisation schedules by December, 2012, 2 Thompson KM Pallansch MA Duintjer Tebbens RJ Wassilak SG Kim J-H Cochi SL Pre-eradication vaccine policy options for poliovirus infection and disease control. Risk Anal. 2013; 33: 516-543 Crossref PubMed Scopus (44) Google Scholar this number has now increased to nearly 90 countries, and during the remainder of 2015, more than 70 countries plan to introduce at least one IPV dose into their immunisation schedules. 3 WHOImmunization Vaccines and Biologicals (IVB), data as of May 1, 2015. http://www.who.int/immunization/diseases/poliomyelitis/endgame_objective2/en/ Google Scholar Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12Fairly few adverse events were reported for the more than 250 million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome reports after IPV were consistent with reporting patterns for other vaccines. No new or unexpected vaccine safety problems were identified for fatal, non-fatal serious, and non-serious reports in this assessment of adverse events after IPV. Full-Text PDF Is introduction of IPV “Good news for billions of children”? – Author's replyThe decision to globally coordinate cessation of use of the oral poliovirus vaccine (OPV), starting with serotype 2 between April 15 and April 30, 2016 (with expected cessation of serotypes 1 and 3 after certification of the world as free of wild polioviruses of those serotypes), represents a crucial step in the effort to end all cases of poliomyelitis.1 After all use of OPV ends, inactivated poliovirus vaccine (IPV) will represent the only option available to protect people from any potential risks of re-introduction of polioviruses. Full-Text PDF Is introduction of IPV “Good news for billions of children”?Mass worldwide vaccination with oral polio vaccine (OPV) has resulted in a steep decrease in polio infections and associated paralysis. Since the world is now close to eradicating polio, vaccine-derived polio constitutes an increasing proportion of overall polio infections. From this perspective, introduction of the more expensive inactivated polio vaccine (IPV) solves a problem as emphasised in the Comment by Kimberley Thompson.1 Full-Text PDF

Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12

Safety data from countries with experience in the use of inactivated poliovirus vaccine (IPV) are important for the global polio eradication strategy to introduce IPV into the immunisation schedules of all countries. In the USA, IPV has been included in the routine immunisation schedule since 1997. We aimed to analyse adverse events after IPV administration reported to the US Vaccine Adverse Event Reporting System (VAERS). We analysed all VAERS data associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as individual or as combination vaccines, for all age and sex groups. We analysed the number and event type (non-serious, non-fatal serious, and death reports) of individual reports, and explored the most commonly coded event terms to describe the adverse event. We classified death reports according to previously published body-system categories (respiratory, cardiovascular, neurological, gastrointestinal, other infectious, and other non-infectious) and reviewed death reports to identify the cause of death. We classified sudden infant death syndrome as a separate cause of death considering previous concerns about sudden infant syndrome after vaccines. We used empirical Bayesian data mining methods to identify disproportionate reporting of adverse events for IPV compared with other vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the safety profiles of IPV and oral poliovirus vaccine (OPV). Of the 41,792 adverse event reports submitted, 39,568 (95%) were for children younger than 7 years. 38,381 of the reports for children in this age group (97%) were for simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for 0·5% of all reports. 34,880 reports were for non-serious events (88%), 3905 reports were for non-fatal serious events (10%), and 783 reports were death reports (2%). Injection-site erythema was the most commonly coded term for non-serious events (29%), and pyrexia for non-fatal serious events (38%). Most deaths (96%) were in children aged 12 months or younger; most (52%) had sudden infant death syndrome as the reported cause of death. The safely profiles of combined IPV and whole-cell pertussis vaccines, OPV and whole-cell pertussis vaccines, and OPV and acellular pertussis vaccines were similar. We noted no indication of disproportionate reporting of adverse events after immunisation with IPV-containing vaccines compared with other vaccines between 1990 and 2013. Fairly few adverse events were reported for the more than 250 million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome reports after IPV were consistent with reporting patterns for other vaccines. No new or unexpected vaccine safety problems were identified for fatal, non-fatal serious, and non-serious reports in this assessment of adverse events after IPV. None.

Modeling strategies to increase population immunity and prevent poliovirus transmission in the high-risk area of northwest Nigeria.

Nigeria continues to struggle in its efforts to eliminate circulating live polioviruses using oral poliovirus vaccine (OPV). We modeled population immunity, and we estimated cases and the timing of transmission die-out for numerous policies that could accelerate the elimination of wild poliovirus type 1 (WPV1) and help Nigeria manage the risks of circulating vaccine-derived polioviruses (cVDPVs). We used a differential-equation based poliovirus transmission and OPV evolution model focused on northwest Nigeria to characterize the impact and trade-offs of potential vaccination strategies, including the introduction of inactivated poliovirus vaccine (IPV). Northwest Nigeria appears close to reaching the threshold of population immunity it must exceed to stop WPV1 transmission if it continues immunizing previously under-vaccinated children. Avoiding type 2 cVDPVs (cVDPV2s) will depend on using sufficient amounts of trivalent OPV, which will also reduce the risks of cVDPV2s after coordinated cessation of type 2-containing OPV (OPV2). Using IPV during the OPV cessation period may increase population immunity, but it leads to a much lower impact on cVDPV risks than ensuring sufficient trivalent OPV use prior to OPV2 cessation. Northwest Nigeria needs to intensify and sustain its immunization efforts to achieve and maintain higher levels of population immunity.