Dose Of Inactivated Poliovirus Vaccine Research Articles

Immune persistence after different polio sequential immunization schedules in Chinese infants

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Effectiveness of poliovirus vaccines against circulating vaccine-derived type 2 poliomyelitis in Nigeria between 2017 and 2022: a case-control study

Between 2018 and 2022, Nigeria experienced continuous transmission of circulating vaccine-derived type 2 poliovirus (cVDPV2), with 526 cases of cVDPV2 poliomyelitis detected in total and approximately 180 million doses of monovalent type 2 oral poliovirus vaccine (mOPV2) and 450 million doses of novel type 2 oral poliovirus vaccine (nOPV2) delivered in outbreak response campaigns. Inactivated poliovirus vaccine (IPV) was introduced into routine immunisation in 2015, with a second dose added in 2021. We aimed to estimate the effectiveness of nOPV2 against cVDPV2 paralysis and compare nOPV2 effectiveness with that of mOPV2 and IPV. In this retrospective case-control study, we used acute flaccid paralysis (AFP) surveillance data in Nigeria from Jan 1, 2017, to Dec 31, 2022, using age-matched, onset-matched, and location-matched cVDPV2-negative AFP cases as test-negative controls. We also did a parallel prospective study from March, 2021, using age-matched community controls from the same settlement as the cases. We included children born after May, 2016, younger than 60 months, for whom polio immunisation history (doses of OPV from campaigns and IPV) was reported. We estimated the per-dose effectiveness of nOPV2 against cVDPV2 paralysis using conditional logistic regression and compared nOPV2 effectiveness with that of mOPV2 and IPV. In the retrospective case-control study, we identified 509 cVDPV2 poliomyelitis cases in Nigeria with case verification and paralysis onset between Jan 1, 2017, and Dec 31, 2022. Of these, 82 children were excluded for not meeting inclusion criteria, and 363 (85%) of 427 eligible cases were matched to 1303 test-negative controls. Cases reported fewer OPV and IPV doses than test-negative controls (mean number of OPV doses 5·9 [SD 4·2] in cases vs 6·7 [4·3] in controls; one or more IPV doses reported in 95 [26%] of 363 cases vs 513 [39%] of 1303 controls). We found low per-dose effectiveness of nOPV2 (12%, 95% CI -2 to 25) and mOPV2 (17%, 3 to 29), but no significant difference between the two vaccines (p=0·67). The estimated effectiveness of one IPV dose was 43% (23 to 58). In the prospective study, 181 (46%) of 392 eligible cases were matched to 1557 community controls. Using community controls, we found a high effectiveness of IPV (89%, 95% CI 83 to 93, for one dose), a low per-dose effectiveness of nOPV2 (-23%, -45 to -5) and mOPV2 (1%, -23 to 20), and no significant difference between the per-dose effectiveness of nOPV2 and mOPV2 (p=0·12). We found no significant difference in estimated effectiveness of the two oral vaccines, supporting the recommendation that the more genetically stable nOPV2 should be preferred in cVDPV2 outbreak response. Our findings highlight the role of IPV and the necessity of strengthening routine immunisation, the primary route through which IPV is delivered. Bill & Melinda Gates Foundation and UK Medical Research Council.

Persistence of immunity following a single dose of inactivated poliovirus vaccine: a phase 4, open label, non-randomised clinical trial

The polio eradication endgame required the withdrawal of Sabin type 2 from the oral poliovirus vaccine and introduction of one or more dose of inactivated poliovirus vaccine (IPV) into routine immunisation schedules. However, the duration of single-dose IPV immunity is unknown. We aimed to address this deficiency. In this phase 4, open-label, non-randomised clinical trial, we assessed single-dose IPV immunity. Two groups of infants or children were screened: the first group had previously received IPV at 14 weeks of age or older (previous IPV group; age >2 years); the second had not previously received IPV (no previous IPV group; age 7-12 months). At enrolment, all participants received an IPV dose. Children in the no previous IPV group received a second IPV dose at day 30. Blood was collected three times in each group: on days 0, 7, and 30 in the previous IPV group and on days 0, 30, and 37 in the no previous IPV group. Poliovirus antibody was measured by microneutralisation assay. Immunity was defined as the presence of a detectable antibody or a rapid anamnestic response (ie, priming). We used the χ2 to compare proportions and the Mann-Whitney U test to assess continuous variables. To assess safety, vaccinees were observed for 30 min, caregivers for each participating child reported adverse events after each follow-up visit and were questioned during each follow-up visit regarding any adverse events during the intervening period. Adverse events were recorded and graded according to the severity of clinical symptoms. The study is registered with ClinicalTrials.gov, NCT03723837. From Nov 18, 2018, to July 31, 2019, 502 participants enrolled in the study, 458 (255 [65%] boys and 203 [44%] girls) were included in the per protocol analysis: 234 (93%) in the previous IPV group and 224 (90%) in the no previous IPV group. In the previous IPV group, 28 months after one IPV dose 233 (>99%) of 234 children had persistence of poliovirus type 2 immunity (100 [43%] of 234 children were seropositive; 133 [99%] of 134 were seronegative and primed). In the no previous IPV group, 30 days after one IPV dose all 224 (100%) children who were type 2 poliovirus naive had seroconverted (223 [>99%] children) or were primed (one [<1%]). No adverse events were deemed attributable to study interventions. A single IPV dose administered at 14 weeks of age or older is highly immunogenic and induces nearly universal type 2 immunity (seroconversion and priming), with immunity persisting for at least 28 months. The polio eradication initiative should prioritise first IPV dose administration to mitigate the paralytic burden caused by poliovirus type 2. WHO and Rotary International.

Vaccine-derived poliovirus serotype 2 outbreaks and response in the Democratic Republic of the Congo, 2017-2021.

Vaccine-derived polioviruses (VDPVs) can emerge from Sabin strain poliovirus serotypes 1, 2, and 3 contained in oral poliovirus vaccine (OPV) after prolonged person-to-person transmission where population vaccination immunity against polioviruses is suboptimal. VDPVs can cause paralysis indistinguishable from wild polioviruses and outbreaks when community circulation ensues. VDPV serotype 2 outbreaks (cVDPV2) have been documented in The Democratic Republic of the Congo (DRC) since 2005. The nine cVDPV2 outbreaks detected during 2005-2012 were geographically-limited and resulted in 73 paralysis cases. No outbreaks were detected during 2013-2016. During January 1, 2017-December 31, 2021, 19 cVDPV2 outbreaks were detected in DRC. Seventeen of the 19 (including two first detected in Angola) resulted in 235 paralysis cases notified in 84 health zones in 18 of DRC's 26 provinces; no notified paralysis cases were associated with the remaining two outbreaks. The DRC-KAS-3 cVDPV2 outbreak that circulated during 2019-2021, and resulted in 101 paralysis cases in 10 provinces, was the largest recorded in DRC during the reporting period in terms of numbers of paralysis cases and geographic expanse. The 15 outbreaks occurring during 2017-early 2021 were successfully controlled with numerous supplemental immunization activities (SIAs) using monovalent OPV Sabin-strain serotype 2 (mOPV2); however, suboptimal mOPV2 vaccination coverage appears to have seeded the cVDPV2 emergences detected during semester 2, 2018 through 2021. Use of the novel OPV serotype 2 (nOPV2), designed to have greater genetic stability than mOPV2, should help DRC's efforts in controlling the more recent cVDPV2 outbreaks with a much lower risk of further seeding VDPV2 emergence. Improving nOPV2 SIA coverage should decrease the number of SIAs needed to interrupt transmission. DRC needs the support of polio eradication and Essential Immunization (EI) partners to accelerate the country's ongoing initiatives for EI strengthening, introduction of a second dose of inactivated poliovirus vaccine (IPV) to increase protection against paralysis, and improving nOPV2 SIA coverage.

Effect of maternal immunisation with multivalent vaccines containing inactivated poliovirus vaccine (IPV) on infant IPV immune response: A phase 4, multi-centre randomised trial

Multivalent diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) has been offered to pregnant women in the United Kingdom since 2012. To assess the impact of maternal DTaP/IPV immunisation on the infant immune response to IPV, we measured poliovirus-specific neutralising antibodies at 2, 5 and 13 months of age in a randomised, phase 4 study of Repevax or Boostrix/IPV in pregnancy and in a non-randomised group born to women not given DTaP/IPV in pregnancy. Infants whose mothers received DTaP/IPV were less likely to seroconvert after three IPV doses than those whose mothers did not receive DTaP/IPV. At 13 months of age, 63/110 (57.2 %), 46/108 (42.6 %) and 40/108 (37.0 %) were seropositive to types 1 to 3, compared with 20/22 (90.9 %), 20/22 (90.9 %) and 14/20 (70.0 %) (p-values 0.003, <0.001 and 0.012). UK infants whose mothers are given DTaP/IPV in pregnancy may be insufficiently protected against poliomyelitis until their pre-school booster.

Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials

Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lead to virulent strains. In this study, we evaluated the genetic and phenotypic stability of shed poliovirus following administration of one dose of monovalent OPV2 (mOPV2) or nOPV2 to infants aged 18-22 weeks. In two similarly designed clinical trials (NCT02521974 and NCT03554798) conducted in Panama, infants aged 18-22-weeks, after immunisation with three doses of bivalent OPV (types 1 and 3) and one dose of inactivated poliovirus vaccine, were administered one or two doses of mOPV2 or nOPV2. In this analysis of two clinical trials, faecally shed polioviruses following one dose of mOPV2 or nOPV2 were isolated from stools meeting predetermined criteria related to sample timing and viral presence and quantity and assessed for nucleotide polymorphisms using next-generation sequencing. A transgenic mouse neurovirulence test was adapted to assess the effect of the possible phenotypic reversion of shed mOPV2 and nOPV2 with a logistic regression model. Of the 91 eligible samples, 86 were able to be sequenced, with 72 evaluated in the transgenic mouse assay. Sabin-2 poliovirus reverts rapidly at nucleotide 481, the primary attenuation site in domain V of the 5' untranslated region of the genome. There was no evidence of neurovirulence-increasing polymorphisms in domain V of shed nOPV2. Reversion of shed Sabin-2 virus corresponded with unadjusted paralysis rates of 47·6% at the 4 log10 50% cell culture infectious dose (CCID50) and 76·7% at the 5 log10 CCID50 inoculum levels, with rates of 2·8% for 4 log10 CCID50 and 11·8% for 5 log10 CCID50 observed for shed nOPV2 samples. The estimated adjusted odds ratio at 4·5 log10 of 0·007 (95% CI 0·002-0·023; p<0·0001) indicates significantly reduced odds of mouse paralysis from virus obtained from nOPV2 recipients compared with mOPV2 recipients. The data indicate increased genetic stability of domain V of nOPV2 relative to mOPV2, with significantly lower neurovirulence of shed nOPV2 virus compared with shed mOPV2. While this vaccine is currently being deployed under an emergency use listing, the data on the genetic stability of nOPV2 will support further regulatory and policy decision-making regarding use of nOPV2 in outbreak responses. Bill & Melinda Gates Foundation.

Inactivated Poliovirus Vaccine Closing the Type 2 Immunity Gap in Vietnam

This was a cross-sectional community-based serological survey of polio antibodies assessing the immunogenicity of inactivated poliovirus vaccine (IPV) focusing on poliovirus serotype 2. IPV was administered to 5-month-old children. Type 2 antibody seroprevalence when measured 1 month after IPV administration was >95%. One IPV dose successfully closed the immunity gap.

Poliomyelitis amidst the COVID-19 pandemic in Africa: Efforts, challenges and recommendations

Poliomyelitis is the leading infectious cause of acute flaccid paralysis among children under five years of age, caused by the Wild Poliovirus, with no medical cure other than prevention through vaccination. The advent of mass vaccination campaigns against polio disease worldwide has greatly decreased the number of global cases and limited the rate of transmission. However, the emergence of Vaccine-derived Poliovirus due to genetic reversions in the live attenuated oral polio vaccine has posed a significant impediment to global polio eradication efforts. Therefore, There is a need to modify the vaccination regimen by utilizing more doses of inactivated poliovirus vaccine or adopting the bivalent oral polio vaccine in order to eliminate the transmission of Vaccine-derived Poliovirus. In addition, collective efforts from governments, health policymakers, vaccination groups and health-related bodies are required to improve vaccine coverage and suppress the circulation of Vaccine-derived Poliovirus.

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

BackgroundThe 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.MethodsWe 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.ResultsA 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.ConclusionsOur 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 RegistrationNCT03890497.

Achieving high immunogenicity against poliovirus with fractional doses of inactivated poliovirus vaccine in Ecuador-results from a cross-sectional serological survey

SummaryBackgroundIn January 2018, Ecuador changed its routine immunization schedule by replacing one full dose of inactivated poliovirus vaccine (IPV) administered intramuscularly at 2 months of age with two doses of fractional IPV (1/5th of full dose, fIPV) administered intradermally at 2 and 4 months of age; and bivalent oral poliovirus vaccine (serotypes 1 and 3, bOPV) continues to be used. We compared seroprevalence and titres of polio antibodies achieved by the past and the current immunization schedules.MethodsThis was a cross-sectional serological survey in children in Ecuador who received bOPV and either one IPV dose in 2017 or two fIPV doses in 2018. One blood sample was collected between October 2020 and March 2021 and analysed for presence of poliovirus neutralizing antibodies at CDC, Atlanta by microneutralization assay.FindingsWe obtained 321 analysable samples from 329 (97·6%) enrolled children (160 received IPV and 161 fIPV). For serotype 2, seroprevalence was 50·0% (CI95%= 44·2-55·8%) for IPV and 83·2% (CI95%=78·5-87·1%) for fIPV recipients (p<0·001). Median antibody titers for serotype 2 were significantly lower for IPV than for fIPV recipients (3·0, CI95%= 3 – 3·5 vs. 4·8, CI95%= 4·5 – 5·2, p<0·001). Seroprevalence for serotypes 1 and 3 was above 90% and was not significantly different between IPV and fIPV recipients.InterpretationEcuador achieved significantly better poliovirus serotype 2 immunogenicity with two fIPV doses than with one IPV dose, while preserving vaccine supply and reducing costs. Our data provide further evidence that fIPV is a beneficial and potentially a cost-effective option in polio immunization.FundingWHO obtained funds for the study from Rotary International.

Microneedle patch as a new platform to effectively deliver inactivated polio vaccine and inactivated rotavirus vaccine.

We recently reported a lack of interference between inactivated rotavirus vaccine (IRV) and inactivated poliovirus vaccine (IPV) and their potential dose sparing when the two vaccines were administered intramuscularly either in combination or standalone in rats and guinea pigs. In the present study, we optimized the formulations of both vaccines and investigated the feasibility of manufacturing a combined IRV-IPV dissolving microneedle patch (dMNP), assessing its compatibility and immunogenicity in rats. Our results showed that IRV delivered by dMNP alone or in combination with IPV induced similar levels of RV-specific IgG and neutralizing antibody. Likewise, IPV delivered by dMNP alone or in combination with IRV induced comparable levels of neutralizing antibody of poliovirus types 1, 2, and 3. We further demonstrated high stability of IRV-dMNP at 5, 25, and 40 °C and IPV-dMNP at 5 and 25 °C, and found that three doses of IRV or IPV when co-administered at a quarter dose was as potent as a full target dose in inducing neutralizing antibodies against corresponding rotavirus or poliovirus. We conclude that IRV-IPV dMNP did not interfere with each other in triggering an immunologic response and were highly immunogenic in rats. Our findings support the further development of this innovative approach to deliver a novel combination vaccine against rotavirus and poliovirus in children throughout the world.

Immunogenicity of Fractional Dose Inactivated Poliovirus Vaccine in India.

IntroductionFollowing the withdrawal of Sabin type 2 from trivalent oral poliovirus vaccine (tOPV) in 2016, the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV) in routine immunization was recommended, either as 1 full dose (0.5mL, intramuscular) or 2 fractional doses of IPV (fIPV—0.1mL, intradermal). India opted for fIPV. We conducted a comparative assessment of IPV and fIPV.MethodsThis was a 4-arm, open-label, multicenter, randomized controlled trial. Infants were enrolled and vaccines administered according to the study design, and the blood was drawn at age 6, 14, and 18 weeks for neutralization testing against all 3 poliovirus types.ResultsStudy enrolled 799 infants. The seroconversion against type 2 poliovirus with 2 fIPV doses was 85.8% (95% confidence interval [CI]: 80.1%-90.0%) when administered at age 6 and 14 weeks, 77.0% (95% CI: 70.5-82.5) when given at age 10 and 14 weeks, compared to 67.9% (95% CI: 60.4-74.6) following 1 full-dose IPV at age 14 weeks.ConclusionThe study demonstrated the superiority of 2 fIPV doses over 1 full-dose IPV in India. Doses of fIPV given at 6 and 14 weeks were more immunogenic than those given at 10 and 14 weeks. Clinical Trial Registry of India (CTRI). Clinical trial registration number was CTRI/2017/02/007793.

Achieving High Immunogenicity Against Poliovirus With Fractional Doses of Inactivated Poliovirus Vaccine in Ecuador

Background: In January 2018, Ecuador changed its routine immunization schedule by replacing one full dose of inactivated poliovirus vaccine (IPV) administered intramuscularly at 2 months of age with two doses of fractional IPV (1/5th of full dose, fIPV) administered intradermally at 2 and 4 months of age; bivalent oral poliovirus vaccine (serotypes 1 and 3, bOPV) continues to be used. We compared seroprevalence and titers of polio antibodies achieved by the past and the current immunization schedules. Methods: This was a cross-sectional serological survey in children in Ecuador who received bOPV and either one IPV dose in 2017 or two fIPV doses in 2018. One blood sample was collected between October 2020 and March 2021 and analysed for presence of poliovirus neutralizing antibodies at CDC, Atlanta by microneutralization assay. Findings: We obtained 321 analyzable samples from 329 (97·6%) enrolled children (160 received IPV and 161 fIPV). For serotype 2, seroprevalence was 50.0% (CI95%= 44·2-55·8%) for IPV and 83·2% (CI95%=78·5-87·1%) for fIPV recipients (p<0·001). Median antibody titers for serotype 2 were significantly lower for IPV than for fIPV recipients (3·0, CI95%= 3 – 3·5 vs. 4·8, CI95%= 4·5 – 5·2, p<0·001). Seroprevalence for serotypes 1 and 3 was above 90% and was not significantly different between IPV and fIPV recipients. Interpretation: Ecuador achieved significantly better poliovirus serotype 2 immunogenicity with two fIPV doses than with one IPV dose, while preserving vaccine supply and reducing costs. Our data provide further evidence that fIPV is a beneficial and cost-effective option in polio immunization. Funding Information: The World Health Organization to the University of San Francisco. Declaration of Interests: All authors – no conflict of interest declared. Ethics Approval Statement: The protocol was reviewed and approved by the Human Research Ethics Committee - CEISH-USFQ and by the Ethics Review Committee at the WHO in Geneva. After obtaining informed consent the children were enrolled.

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.

Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation, an open label, phase IV, randomized controlled trial

BackgroundAfter global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age. MethodsWe conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age. FindingsOf the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77–81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98–99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C. InterpretationResults support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.

Adverse events following immunization with bivalent oral poliovirus vaccine in Jiangsu, China.

The bivalent oral poliovirus vaccine (bOPV; Sabin types 1 and 3) replaced the trivalent OPV (Sabin types 1, 2 and 3) globally in April 2016. A routine schedule of 1 dose of inactivated poliovirus vaccine and 3 subsequent doses of bOPV was implemented in Jiangsu simultaneously. The schedule was changed to 2 inactivated poliovirus vaccines + 2 bOPV on 1 September 2019. Although OPV type 2 has been removed, challenges persist because of adverse events following immunization (AEFIs) with bOPV. Therefore, we analysed and evaluated the safety profile of bOPV administered in children based on passive postmarketing AEFI surveillance. We collected all bOPV-related AEFI reports in Jiangsu from the Chinese National AEFI Information System (CNAEFIS) between May 2016 and April 2020. We obtained the administered doses of bOPV from the Jiangsu Provincial Electronic Immunization Registries System. A descriptive analysis was performed. In total, 2084 bOPV-related AEFIs were retrieved from the CNAEFIS. The overall reporting rate was 24.16 per 100 000 doses. Most AEFIs were nonserious. The most frequently reported symptoms were fever, rash and gastrointestinal disorders. Only 1.34% of AEFIs were serious, which thrombocytopenic purpura accounted for the largest category. Seventeen serious adverse events, including 2 vaccine-associated paralytic poliomyelitis (VAPP) cases, were considered to be related to bOPV vaccination. The rate of VAPP was 0.2 per million doses. AEFI analysis showed that bOPV was well tolerated. The events most frequently reported were nonserious. However, bOPV can still cause VAPP. Attention should be given to risks related to bOPV.

Fractional dose compared with standard dose inactivated poliovirus vaccine in children: a systematic review and meta-analysis

Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV (fIPV) administration is one of the strategies to ensure IPV availability. We reviewed studies comparing the effects of fractional with full-dose IPV vaccination to determine when seroconversion proportions with each strategy become similar in children aged 5 years and younger. In this systematic review and meta-analysis, we searched 16 databases in July, 2019, for trials and observational studies, including ongoing studies that compare immunogenicity and adverse events of fractional-dose (0·1 mL) to full-dose (0·5 mL) IPV in healthy children aged 5 years or younger regardless of study design, number of doses, and route of administration. Screening, selection of articles, data extraction, and risk of bias assessment were done in duplicate, and conflicts were resolved by discussion or arbitration by a third author. We assessed immunogenicity, the main outcome, as proportion of seroconverted participants and changes in geometric mean titres of anti-poliovirus antibodies. Timepoints were eligible for analysis if measurements were done at least 4 weeks after vaccination. Summary estimates were pooled by use of random-effects meta-analysis. Analysis was stratified by study design, type of outcome measure, type of poliovirus, and number of doses given. We assessed heterogeneity using the χ2 test of homogeneity and quantified it using the I2 statistic. We assessed risk of bias using the Cochrane risk of bias tool, and the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The study is registered with PROSPERO, CRD42018092647. 860 records were screened for eligibility, of which 36 potentially eligible full-text articles were assessed and 14 articles were included in the final analysis: two ongoing trials and 12 articles reporting on ten completed studies. For poliovirus type 2, there were no significant differences in the proportions of seroconversions between fractional and full doses of IPV for two or three doses: the risk ratio for serconversion at one dose was 0·61 (95% CI 0·51-0·72), at two doses was 0·90 (0·82-1·00), and at three doses was 0·95 (0·91-1·00). Geometric mean titres (GMTs) for poliovirus type 2 were lower for fIPV than for full-dose IPV: -0·51 (95% CI -0·87 to -0·14) at one dose, -0·49 (-0·70 to -0·28) at two doses, and -0·98 (-1·46 to -0·51) at three doses. The seroconversion meta-analysis for the three-dose comparison was homogeneous (p=0·45; I2=0%), whereas heterogeneity was observed in the two-dose (p<0·00001; I2=88%) and one-dose (p=0·0004; I2=74%) comparisons. Heterogeneity was observed in meta-analyses of GMTs for one-dose (p<0·00001; I2=92%), two-dose (p=0·002; I2=80%), and three-dose (p<0·00001; I2=93%) comparisons. Findings for types 1 and 3 were similar to those for type 2. The certainty of the evidence was high for the three-dose comparisons and moderate for the rest of the comparisons. There is no substantial difference in seroconversion between three doses of fIPV and three doses of full-dose IPV, although the full dose gives higher titres of antibodies for poliovirus type 1, 2, and 3. Use of fractional IPV instead of the full dose can stretch supplies and possibly lower the cost of vaccination. South African Medical Research Council and the National Research Foundation of South Africa.

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.

Health and Economic Outcomes Associated with Polio Vaccine Policy Options: 2019-2029.

The polio endgame remains complicated, with many questions about future polio vaccines and national immunization policies. We simulated possible future poliovirus vaccine routine immunization policies for countries stratified by World Bank Income Levels and estimated the expected costs and cases using an updated integrated dynamic poliovirus transmission, stochastic risk, and economic model. We consider two reference cases scenarios: one that achieves the eradication of all wild polioviruses (WPVs) by 2023 and one in which serotype 1 WPV (WPV1) transmission continues. The results show that the addition of inactivated poliovirus vaccine (IPV) to routine immunization in all countries substantially increased the expected costs of the polio endgame, without substantially increasing its expected health or economic benefits. Adding a second dose of IPV to the routine immunization schedules of countries that currently include a single IPV dose further increases costs and does not appear economically justified in the reference case that does not stop WPV transmission. For the reference case that includes all WPV eradication, adding a second IPV dose at the time of successful oral poliovirus vaccine (OPV) cessation represents a cost-effective option. The risks and costs of needing to restart OPV use change the economics of the polio endgame, although the time horizon used for modeling impacts the overall economic results. National health leaders will want to consider the expected health and economic net benefits of their national polio vaccine strategies recognizing that preferred strategies may differ.

Current polio status in the world

ABSTRACT Poliomyelitis is still an endemic disease in Afghanistan, Nigeria, and Pakistan despite the efforts to eradicate the disease. Therefore, there is a potential risk of international spread. Since the start of the polio eradication program by the Global Polio Eradication Initiative in 1988, the incidence of polio has been reduced by 99%. In the last decade, wild poliovirus type 2 (WPV2) was eliminated and declared eradicated in 2015. Wild poliovirus type 3 (WPV3) was last reported in November 2012. These changes have allowed the removal of Sabin poliovirus type 2 from the oral poliovirus vaccine (OPV) in April 2016 and countries either introduced bivalent OPV (bOPV) containing Sabin types 1 + 3 poliovirus or added at least one dose of inactivated poliovirus vaccine (IPV) into their routine immunization schedule. Many efforts are needed to eradicate polio, and new strategies should be implemented such as the development and approval of new genetically stable OPV, and vaccines that do not require infectious processes for virus growth, such as virus-like particles (VLPs), or packing-cell technology. IPV will increasingly be produced from Sabin strains, and further attenuated or genetically modified strains. Furthermore, there is also a need for the development of antiviral drugs to treat immunodeficient patients who are long-term excretors infected with poliovirus, thus avoiding contamination of individuals susceptible to polioviruses, due to reversal of pathogenicity. If all these measures are successfully implemented, the world will be close to the global