The Immunogenicity of Fractional Intradermal doses of the Inactivated Poliovirus Vaccine is Associated with the Size of the Intradermal Fluid Bleb

The global effort to eradicate polio is in its final stages. Research findings published in Clinical Infectious Diseases, Oxford Academic, shows that the immunogenicity of fractional (1/5th, 0.1mL) intradermal doses of the inactivated poliovirus vaccine (ID fIPV) is positively correlated with the size of the intradermal fluid bleb. Findings also suggest that training of vaccinators for the campaign and routine ID fIPV administration should focus on generating an 8 to 10mm bleb with each injection.

Child being immunised with inactivated poliovirus vaccine

Child being immunised with inactivated poliovirus vaccine

The clinical trial was undertaken to examine the immunogenicity of ID fIPV and the use of disposable syringe jet injectors (DSJI) to deliver IPV in nine and ten-month old infants in The Gambia. The study was conducted by a team of scientists from MRC Unit The Gambia, funded by the Bill & Melinda Gates Foundation and by the MRC (UK).

While previous studies have confirmed the immunogenicity of ID fIPV; the per dose seroconversion rates and geometric mean neutralizing antibody titres are consistently lower than those generated by a full (0.5mL) intramuscular (IM) dose of the same vaccine. This nested study provides definitive data on the effect of ID fluid bleb size on the immunogenicity of ID fIPV and should be used as a basis for current training and vaccination practice.

700 (nine and ten months old) infants were recruited and randomized into one of the four groups and provided data for analysis in this study. Thus, 65.8% of infants with a bleb size of 8 to 10mm seroconverted or had a four-fold rise in antibody titres to serotype 1 compared with 66.5% of those who received a full IM dose of the vaccine. The immune responses to ID fIPV in infants with an 8 to 10mm fluid bleb were comparable to those generated by a full IM dose of the same vaccine.

Findings show a significant reduction in serotype 2 immunogenicity associated with increasing volumes of fluid lost onto the skin when the data for all ID vaccinations was analysed. The equivalent figures for serotype 2 were 58.8% by the ID route compared with 66.2% by the IM route and for serotype 3, 86.0% by the ID route compared with 81.8% by the IM route. Of the 700 infants, 177 each received ID fIPV using a needle and syringe and a DSJI.

When asked to comment on the findings Prof Beate Kampmann, Theme Leader, Vaccines and Immunity Theme said “this data comes at a crucial time to inform the polio endgame strategies: doses of IPV are now recommended as part of EPI, and the large quantity required has led to a supply shortage. Hence the immunogenicity of smaller (fractional) dosing is being explored to make sure everyone gets a protective dose. I am proud of the team and the MRCG contribution to provide a solid evidence base from this large scale trial of how such fractional doses could be best used. The data generated by Dr Clarke and the polio study team were shared with WHO and have already had a direct impact on planning for polio campaigns and the required training for health care workers to administer  IPV.”

Read more about the findings at Oxford Academic on https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cix381

 

Acknowledgements

We thank Dr Kevin Brown and the staff of the Immunization and Diagnostic and Enteric Virus Units within the Virus Reference Department, Public Health England (Colindale, UK) for conducting the serological testing; the Nederland Vaccine Institute for the donation of the IPV vaccine; Pharma Jet who were contracted to supply the DSJI devices and to provide certified training; Laura Saganic, Gene Saxon and Darin Zehrung from Programe for Appropriate Technology in Health (PATH) for their contribution to the device evaluation methodology; The Government of The Gambia, Ministry of Health and Social Welfare and Expanded Programme on Immunization office and regional health teams for their support; all other MRCG staff who assisted with the study in any way and the infants and families who took part in the study.

Authors

Jack Bibby, Yauba Saidu, Ama Umesi, Ngozi Moneke-Anyanwoke1, Adedapo O Bashorun, Mariama Badjie Hydara, Ikechukwu Adigweme, Jane U Adetifa, Michael Okoye, Elishia Roberts, Ralf Clemens, Ananda S Bandyopadhyay, Abdul K Muhammad, Sarah Mulwa, Michael Royals, Courtney Jarrahian, David Jeffries, Beate Kampmann, Ed Clarke.