Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Bandyopadhyay AS

PROVIDER: S-EPMC7781454 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

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.

Bandyopadhyay Ananda S AS Gast Chris C Brickley Elizabeth B EB Rüttimann Ricardo R Clemens Ralf R Oberste M Steven MS Weldon William C WC Ackerman Margaret E ME Connor Ruth I RI Wieland-Alter Wendy F WF Wright Peter P Usonis Vytautas V

The Journal of infectious diseases 20210101 1

<h4>Background</h4>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.<h4>Methods</h4>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 mOP ...[more]

PMID: 32621741

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Project description:The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions: The fractional dose with one-fifth (1/5) could be used by intradermal injection to prevent poliovirus infection, if there were more human clinical detail research consistent with this findings in rats.

Project description:BackgroundTo inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV).MethodsWe conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004).FindingsDuring 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines.InterpretationGiven with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV.FundingU.S. Centers for Disease Control and Prevention.

Project description:BackgroundMonovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2.MethodsWe did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 105 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual.FindingsBetween Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune responses after two mOPV2 doses were observed in 161 (93%) of 173 infants with testable serum samples in the 1 week group, 169 (96%) of 177 in the 2 week group, and 176 (97%) of 181 in the 4 week group. 1 week and 2 week intervals between two mOPV2 doses were non-inferior to 4 week intervals because the lower bound of the absolute differences in the percentage of immune responses were greater than -10% (-4·2% [90% CI -7·9 to -0·4] in the 1 week group and -1·8% [-5·0 to 1·5] in the 2 week group vs the 4 week group). The immune response elicited by two mOPV2 doses 4 weeks apart was not different when IPV was added to the first dose (176 [97%] of 182 infants with IPV vs 176 [97%] of 181 without IPV; p=1·0). During the trial, two serious adverse events (pneumonia; one [1%] of 186 patients in the 1 week group and one [1%] of 182 in the 4 week group) and no deaths were reported; the adverse events were not attributed to the vaccines.InterpretationAdministration of mOPV2 at short intervals does not interfere with its immunogenicity. The addition of IPV to the first mOPV2 dose did not improve poliovirus type 2 immune response.FundingUS Centers for Disease Control and Prevention.

Project description:BackgroundWe assessed immunogenicity of three-dose and two-dose immunization schedules with a Sabin-strain inactivated poliovirus vaccine (sIPV) produced by one Chinese vaccine manufacturer.MethodsThis was an open label, randomized, controlled trial conducted in 16 vaccination clinics in Shandong province. Infants were allocated randomly to either a 3-dose study arm (sIPV administered at 2, 3, and 4 months of age) or a 2-dose arm (sIPV administered at 4 and 8-11 months of age). Poliovirus neutralizing antibodies were measured in sera collected prior to the first sIPV dose and one month after the last dose.FindingsWe enrolled 560 infants; 536 (95.7%) completed the study. Final seropositivity rates were >98% for all three serotypes in both study arms. There were no statistically significant differences in seropositivity between the 2-dose and the 3-dose schedule. Final median reciprocal titres of polio antibodies were high overall (>1:768 for all serotypes) and statistically significantly higher in 2-dose recipients compared with 3-dose recipients (p < 0.001).InterpretationThis study offers evidence that two doses of sIPV administered at 4 and 8-11 months of age and three doses of sIPV administered at 2, 3, and 4 months of age both provide serological protection against poliomyelitis. Median reciprocal titres of polio antibodies were high overall, and were more related to the interval between doses than the number of doses, with the longer interval of the 2-dose schedule producing higher reciprocal titres than the shorter-interval 3-dose schedule. The protection provided by the 3-dose schedule is achieved earlier in life than the protection with the 2-dose schedule. Countries planning to use an IPV-only schedule in the post-eradication era can consider this 2-dose sIPV option as an immunogenic and dose-sparing strategy.FundingWorld Health Organization (from a grant from International PolioPlus Committee, Rotary International, Evanston, IL, USA).

Project description:BackgroundContinued emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin oral poliovirus vaccines (OPVs) has stimulated development of two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence. We aimed to assess safety and immunogenicity of the two novel OPV candidates compared with a monovalent Sabin OPV in children and infants.MethodsWe did two single-centre, multi-site, partly-masked, randomised trials in healthy cohorts of children (aged 1-4 years) and infants (aged 18-22 weeks) in Panama: a control phase 4 study with monovalent Sabin OPV2 before global cessation of monovalent OPV2 use, and a phase 2 study with low and high doses of two novel OPV2 candidates. All participants received one OPV2 vaccination and subsets received two doses 28 days apart. Parents reported solicited and unsolicited adverse events. Type 2 poliovirus neutralising antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days post-vaccination. Primary objectives were to assess safety in all participants and non-inferiority of novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants (non-inferiority margin 10%). These studies were registered with ClinicalTrials.gov, NCT02521974 and NCT03554798.FindingsThe control study took place between Oct 23, 2015, and April 29, 2016, and the subsequent phase 2 study between Sept 19, 2018, and Sept 30, 2019. 150 children (50 in the control study and 100 of 129 assessed for eligibility in the novel OPV2 study) and 684 infants (110 of 114 assessed for eligibility in the control study and 574 of 684 assessed for eligibility in the novel OPV2 study) were enrolled and received at least one study vaccination. Vaccinations were safe and well tolerated with no causally associated serious adverse events or important medical events in any group. Solicited and unsolicited adverse events were overwhelmingly mild or moderate irrespective of vaccine or dose. Nearly all children were seroprotected at baseline, indicating high baseline immunity. In children, the seroprotection rate 28 days after one dose was 100% for monovalent OPV2 and both novel OPV2 candidates. In infants at day 28, 91 (94% [95% CI 87-98]) of 97 were seroprotected after receiving monovalent OPV2, 134 (94% [88-97]) of 143 after high-dose novel OPV2-c1, 122 (93% [87-97]) of 131 after low-dose novel OPV2-c1, 138 (95% [90-98]) of 146 after high-dose novel OPV2-c2, and 115 (91% [84-95]) of 127 after low-dose novel OPV2-c2. Non-inferiority was shown for low-dose and high-dose novel OPV2-c1 and high-dose novel OPV2-c2 despite monovalent OPV2 recipients having higher baseline immunity.InterpretationBoth novel OPV2 candidates were safe, well tolerated, and immunogenic in children and infants. Novel OPV2 could be an important addition to our resources against poliovirus given the current epidemiological situation.FundingFighting Infectious Diseases in Emerging Countries and Bill & Melinda Gates Foundation.

Project description:ImportanceThe Sabin-strain inactivated poliovirus vaccine (IPV) may be a tool for polio outbreak response in certain situations.ObjectiveTo investigate the response to a type 2 vaccine-derived poliovirus (VDPV2) outbreak.Design, setting, and participantsThis case series was conducted in China after a VDPV2 was detected in stool specimens from a child with acute flaccid paralysis (AFP) in Sichuan Province in 2019, 3 years after the global withdrawal of live, attenuated type 2 oral poliovirus vaccine (OPV). Investigation followed National Health Commission and World Health Organization guidance and included searching hospitals for unreported AFP cases; testing stool specimens from the child, his contacts, and local children; enhanced environmental surveillance for VDPV2s in wastewater; and measuring vaccination coverage. Sabin-strain IPV campaigns were conducted in a wide geographic area.Main outcomes and measuresAny VDPV2 detection after completion of the supplementary immunization activities.ResultsA 28-nucleotide-change VDPV2 was isolated from a young boy. Three VDPV2s were detected in healthy children; 2 were contacts of the original child, and none had paralysis. A search of 31 million hospital records found 10 unreported AFP cases; none were polio. No type 2 polioviruses were found in wastewater. Prior to the event, polio vaccine coverage was 65% among children younger than 5 years. Sabin-strain IPV campaigns reached more than 97% of targeted children, administering 1.4 million doses. No transmission source was identified. More than 1 year of enhanced poliovirus environmental and AFP surveillance detected no additional VDPVs.Conclusions and relevanceThese findings suggest that the circulating VPDV2 outbreak in 2019 was associated with low vaccine coverage. An investigation discovered 3 infected but otherwise healthy children and no evidence of the virus in wastewater. Following Sabin-strain IPV-only campaigns expanding from county to prefecture, the poliovirus was not detected, and the outbreak response was considered by an expert panel and the World Health Organization to have been successful. This success suggests that the Sabin-strain IPV may be a useful tool for responding to circulating VDPV2 outbreaks when high-quality supplementary immunization activities can be conducted and carefully monitored in settings with good sanitation.

Dataset Information

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

Methods

Results

Conclusions

Publications

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.

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