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Reduced mucosal immunity to poliovirus after cessation of trivalent oral polio vaccine.

ABSTRACT: The switch from using only trivalent oral polio vaccine (tOPV) to sequential schedules combining inactivated poliovirus vaccine (IPV) and bivalent oral polio vaccine (bOPV) for polio vaccination will cause changes to mucosal immunity against polio in infants, which plays an important role in preventing the poliovirus spread. Here, we analyzed mucosal immunity against poliovirus in the intestine during different sequential vaccination schedules. We conducted clinical trials in Guangxi Province, China on 1,200 2-month-old infants who were randomly assigned to one of three vaccination schedule groups: IPV-bOPV-bOPV, IPV-IPV-tOPV, and IPV-IPV-bOPV, with vaccine doses administered at 8, 12, and 16 weeks of age. Stool samples were collected from 10% of participants in each group before administration of the second vaccine doses and at 1, 2, and 4 weeks after the administrations of the second and third vaccine doses. Immunoglobulin A (IgA) in the stool samples was measured to analyze the mucosal immune response in the intestine. Because of the absence of poliovirus type 2 in bOPV, the vaccination schedule of IPV-IPV-bOPV did not sufficiently raise intestinal mucosal immunity against poliovirus type 2, although some cross-immunity was seen. The level of intestinal mucosal immunity was related to shedding status; shedders could produce intestinal mucosa IgA more quickly. The intestinal mucosal immunity level was not related to serum neutralizing antibody level. In the combined sequential vaccination schedule of IPV and bOPV, the risk of circulating vaccine-derived poliovirus type 2 (cVDPV2) may be increased owing to insufficient intestinal mucosal immunity against poliovirus type 2.

SUBMITTER: Zhao T

PROVIDER: S-EPMC8475588 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTrivalent oral polio vaccine (tOPV) was replaced worldwide from April, 2016, by bivalent types 1 and 3 oral polio vaccine (bOPV) and one dose of inactivated polio vaccine (IPV) where available. The risk of transmission of type 2 poliovirus or Sabin 2 virus on re-introduction or resurgence of type 2 poliovirus after this switch is not understood completely. We aimed to assess the risk of Sabin 2 transmission after a polio vaccination campaign with a monovalent type 2 oral polio vaccine (mOPV2).MethodsWe did an open-label cluster-randomised trial in villages in the Matlab region of Bangladesh. We randomly allocated villages (clusters) to either: tOPV at age 6 weeks, 10 weeks, and 14 weeks; or bOPV at age 6 weeks, 10 weeks, and 14 weeks and either one dose of IPV at age 14 weeks or two doses of IPV at age 14 weeks and 18 weeks. After completion of enrolment, we implemented an mOPV2 vaccination campaign that targeted 40% of children younger than 5 years, regardless of enrolment status. The primary outcome was Sabin 2 incidence in the 10 weeks after the campaign in per-protocol infants who did not receive mOPV2, as assessed by faecal shedding of Sabin 2 by reverse transcriptase quantitative PCR (RT-qPCR). The effect of previous immunity on incidence was also investigated with a dynamical model of poliovirus transmission to observe prevalence and incidence of Sabin 2 virus. This trial is registered at ClinicalTrials.gov, number NCT02477046.FindingsBetween April 30, 2015, and Jan 14, 2016, individuals from 67 villages were enrolled to the study. 22 villages (300 infants) were randomly assigned tOPV, 23 villages (310 infants) were allocated bOPV and one dose of IPV, and 22 villages (329 infants) were assigned bOPV and two doses of IPV. Faecal shedding of Sabin 2 in infants who did not receive the mOPV2 challenge did not differ between children immunised with bOPV and one or two doses of IPV and those who received tOPV (15 of 252 [6%] vs six of 122 [4%]; odds ratio [OR] 1·29, 95% CI 0·45-3·72; p=0·310). However, faecal shedding of Sabin 2 in household contacts was increased significantly with bOPV and one or two doses of IPV compared with tOPV (17 of 751 [2%] vs three of 353 [1%]; OR 3·60, 95% CI 0·82-15·9; p=0·045). Dynamical modelling of within-household incidence showed that immunity in household contacts limited transmission.InterpretationIn this study, simulating 1 year of tOPV cessation, Sabin 2 transmission was higher in household contacts of mOPV2 recipients in villages receiving bOPV and either one or two doses of IPV, but transmission was not increased in the community as a whole as shown by the non-significant difference in incidence among infants. Dynamical modelling indicates that transmission risk will be higher with more time since cessation.FundingBill & Melinda Gates Foundation.

Project description:BackgroundMass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses.MethodsWe analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine-derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2.ResultsThe prevalence of Sabin-2 poliovirus in stool samples declined from 3.9% (95% confidence interval [CI], 3.5 to 4.3) at the time of OPV2 withdrawal to 0.2% (95% CI, 0.1 to 2.7) at 2 months after withdrawal, and the detection rate in sewage samples declined from 71.0% (95% CI, 61.0 to 80.0) to 13.0% (95% CI, 8.0 to 20.0) during the same period. However, 12 months after OPV2 withdrawal, Sabin-2 poliovirus continued to be detected in stool samples (<0.1%; 95% CI, <0.1 to 0.1) and sewage samples (8.0%; 95% CI, 5.0 to 13.0) because of the use of OPV2 in response to VDPV2 outbreaks. Nine outbreaks were reported after OPV2 withdrawal and were associated with low coverage of routine immunization (odds ratio, 1.64 [95% CI, 1.14 to 2.54] per 10% absolute decrease) and low levels of population immunity (odds ratio, 2.60 [95% CI, 1.35 to 5.59] per 10% absolute decrease) within affected countries.ConclusionsHigh population immunity has facilitated the decline in the prevalence of Sabin-2 poliovirus after OPV2 withdrawal and restricted the circulation of VDPV2 to areas known to be at high risk for transmission. The prevention of VDPV2 outbreaks in these known areas before the accumulation of substantial cohorts of children susceptible to type 2 poliovirus remains a high priority. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization.).

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Reduced mucosal immunity to poliovirus after cessation of trivalent oral polio vaccine.

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