Intradermal administration of fractional doses of the inactivated poliovirus vaccine in a campaign: a pragmatic, open-label, non-inferiority trial in The Gambia

Abstract

Background: A rapid increase in circulating vaccine-derived poliovirus type 2 outbreaks, and the need to reserve inactivated poliovirus vaccine (IPV) for routine immunisation, has increased the value of fractional dose IPV (fIPV) as a measure to prevent acute flaccid paralysis. However, the intradermal route of administration has been viewed as prohibitive to outbreak response campaigns. We aimed to establish the immunogenicity and safety of administering intradermal fIPV with a disposable syringe jet injector (DSJI) or an intradermal adaptor (IDA) compared with standard administration with a BCG needle and syringe (N&S).

Methods: This pragmatic, non-inferiority trial was undertaken in a campaign setting in communities in The Gambia. Children aged 4-59 months without contraindication to vaccination were eligible. Children were not individually randomly assigned; instead, the vaccination teams were randomly assigned (1:1:1) to one of three administration methods. Parents and the field team were not masked, but laboratory personnel were masked. Baseline demographic and anthropometric data were collected from the participants. Public health officers experienced at intradermal immunisation, and nurses without experience, had 2 h of training on each of the administration methods before the campaign. Participants were vaccinated using the administration method in use by the vaccination team in their community. Poliovirus serum neutralising antibodies (SNA) were measured in children aged 24-59 months before and 4 weeks after vaccination. Adverse events and data on injection quality were collected from all participants. The primary outcome was the type 2 immune response rate (seroconversion in seronegative [SNA titre <8] children plus a 4-fold titre rise in seropositive children). Adjusted differences in the immune response between the DSJI or IDA group versus the N&S group were calculated with 97·5% CIs. A margin of -10% was used to define the non-inferiority of DSJI or IDA compared to N&S. Immunogenicity analysis was done per protocol. The trial is registered with ClinicalTrials.govNCT02967783 and has been completed.

Findings: Between Oct 28 and Dec 29, 2016, 3189 children aged 4-59 months were recruited, of whom 3170 were eligible. Over 3 days, 2720 children were vaccinated (N&S, 917; IDA, 874; and DSJI, 929). Among 992 children aged 25-59 months with a baseline SNA available, 90·1% (95% CI 86·1-92·9; 281/312) of those vaccinated using the DSJI had an immune response to type 2 compared with 93·8% (90·6-95·8; 331/353) of those vaccinated with N&S and 96·6% (94·0-98·0; 316/327) of those vaccinated with IDA. All (53/53) type 2 seronegative children seroconverted. For polio type 2, non-inferiority was shown for both the IDA (adjusted difference 0·7% [97·5% CI -3·3 to 4·7], unadjusted difference 2·9% [-0·9 to 6·8]) and DSJI (adjusted difference -3·3% [-8·3 to 1·5], unadjusted difference -3·7% [-8·7 to 1·1]) compared with N&S. Non-inferiority was shown for type 1 and 3 for the IDA and DSJI. Neither injection quality nor the training and experience of the vaccinators had an effect on immune response. No safety concerns were reported.

Interpretation: In a campaign, intradermal fIPV is safe and generates consistent immune responses that are not dependent on vaccinator experience or injection quality when administered using an N&S, DSJI, or IDA. Countries facing vaccine-derived poliovirus type 2 outbreaks should consider fIPV campaigns to boost population immunity and prevent cases of acute flaccid paralysis.

Funding: World Health Organization and the Medical Research Council.

Conflict of interest statement

Declaration of interests We declare no competing interests.

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1

Trial profile Figure illustrating the number of infants and children who took part in the campaign separated into those aged 4–23 months and 24–59 months. Serological analysis (baseline and post-vaccination serum neutralising antibody titres for poliovirus types 1, 2, and 3) was only undertaken in those aged 24–59 months. DSJI=disposable syringe jet injector. IDA=intradermal adapter. N&S=needle and syringe.

Figure 2

Distribution of SNA titres Reverse cumulative distribution curves illustrating the distribution of poliovirus type 1, poliovirus type 2, and poliovirus type 3 SNA titres at baseline and post-vaccination after the administration of an intradermal fractional dose of inactivated poliovirus vaccine using N&S, DSJI, or IDA. DSJI=disposable syringe jet injector. IDA=intradermal adapter. N&S=needle and syringe. SNA=serum neutralising antibody.

Figure 3

Effects of administration method on type-specific immune responses Differences in the percentage of participants having an immune response to poliovirus type 1, poliovirus type 2, or poliovirus type 3 after the administration of an intradermal fractional dose of inactivated poliovirus vaccine via IDA or DSJI, compared with the reference N&S method. The percentage of children who had an immune response after intradermal fractional dose inactivated poliovirus vaccine was calculated combining the percentage who underwent seroconversion (baseline SNA titres of 362 were excluded from the analysis because a four-fold rise was beyond the upper limit of quantification the assay (table 3). Point estimates and 97·5% CI are illustrated. The 97·5% CI were adjusted for age, sex, and variables associated with the immune response in a multivariable regression model developed for each type (type 1: baseline seropositivity, appendix p 8; type 2: number of previous oral poliovirus vaccine doses, time taken to vaccinate, maternal occupation, appendix p 9; type 3: baseline seropositivity, appendix p 10). DSJI=disposable syringe jet injector. IDA=intradermal adapter. N&S=needle and syringe. SNA=serum neutralising antibody.