Use of traditional serological methods and oral fluids to assess immunogenicity in children aged 2–16 years after successive annual vaccinations with LAIV

Katja Hoschler*, Sunil Maharjan, Heather Whitaker, Joanna Southern, Blessing Okai, Janice Baldevarona, Paul J. Turner, Nicholas Andrews, Elizabeth Miller, Maria Zambon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: The UK introduced quadrivalent live attenuated influenza vaccine (qLAIV) for children in 2013/2014. The impact of annual vaccination on effectiveness and immunogenicity is being assessed. Method: A phase III/IV open-label study of the immunogenicity of annual vaccination with qLAIV (Fluenz™) was conducted over three consecutive years (2014/15–2016/17) in 254, 249 and 162 children respectively. Serum responses to vaccine components were measured by Haemagglutination Inhibition (HAI) and anti-A(H1N1)pdm09 Neuraminidase (NAI) assays, stratified according to previous receipt of AS03B-adjuvanted A(H1N1)pdm09 pandemic vaccine in 2009/10. Antibody levels to the A(H1N1)pdm09 and H3N2 vaccine components in oral fluids (OF) were explored using an ELISA. Findings: More paired pre- and post-vaccination oral fluids (96%) than paired sera (87%) were obtained. Geometric mean titre rises using HAI assays were limited, with maximum rises seen in year one for both influenza B strains when 39% and 43% of subjects seroconverted (95% confidence interval 33–46% and 36–50%, respectively) and year two for influenza H3N2, when 40% (33–46%) individuals seroconverted. Prior pandemic vaccine receipt resulted in higher pre- and post-vaccination A(H1N1)pdm09 HAI titres and lower pre-and post-vaccination NAI (N1 neuraminidase) titres in all three years. OF results were congruent with HAI results; assay specificity compared to HAI was 88.1 and 71.6 percent, and sensitivity was 86.4 and 74.8 percent respectively for A(H1N1)pdm09 and H3N2. Conclusion: In all three study years, vaccination with qLAIV resulted in poor antibody responses. However, OFs are an alternative specimen type that allows self sampling, can easily be obtained from children, and their analysis leads to similar conclusions as classic serology by HAI. Their suitability for seroprevalence studies should be investigated. We demonstrated a sustained effect from prior receipt of the AS03B-adjuvanted A(H1N1)pdm09 vaccine, even after repeat vaccination with qLAIV indicating that early exposure to influenza antigens has a significant long lasting effect.

Original languageEnglish
Pages (from-to)2660-2670
Number of pages11
JournalVaccine
Volume38
Issue number12
DOIs
Publication statusPublished - 10 Mar 2020

Bibliographical note

Funding Information:
We thank Max Pitcher and Kourtney Wilson for their technical support at the Respiratory Virus Unit (PHE NIS, Colindale) and are especially grateful to Christine Carr, Sammy Ho and Monali Patel for their contribution to assay validation and automation of OF, total IgG ELISA and NAI assays and to Catherine Thompson who optimised some of the methods used in the laboratory analyses for NA antibody assay. We thank Prof Richard Tedder, Ruth Parry, Prof Kevin Brown and Lenesha Warrener for useful discussions about the use of oral fluids and are grateful to Pravesh Dhanilall and the team in Immunisation and Diagnosis Unit (IDU, PHE) for the provision of their in-house ELISA protocol for quantification of total IgG in Oral Fluids. We thank the Vaccine Research Nurses in Hertfordshire and Gloucestershire for the recruitment and follow-up of the majority of study participants and HPRU nurses Khatiba Raja and Helen Piotrowski for their assistance, Mrs Pauline Kaye for database design and data management and staff in the Immunisation Department for study administration and data entry. This work was funded by the NIHR Policy Research Programme (National Vaccine Evaluation Consortium, Grant number 039/0031- grant holder EM) and by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections at Imperial College London in partnership with Public Health England (PHE), collaborating with Ajit Lalvani. Sunil Maharjan and Blessing Okai were affiliated to the NIHR HPRU in Respiratory Infections and both based at the National Infection Service, Public Health England during this work. The views expressed in the publication are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health, arms? length bodies, other government departments. JS & MZ drafted the protocol, JS obtained all governance approvals and oversaw the field work and data entry. PJT provided clinical support. JB, together with KH prepared and organised the laboratory analysis of trial samples, SM and BO developed the OF assays, KH directed the laboratory testing, was involved in data interpretation and produced the first draft of the paper. HW, FW and NA conducted the statistical analysis. EM, MZ designed the study and with NA directed the analyses and interpretation of the results. All authors contributed to, reviewed and approved the final draft of the manuscript.

Funding Information:
This work was funded by the NIHR Policy Research Programme ( National Vaccine Evaluation Consortium , Grant number 039/0031 - grant holder EM) and by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections at Imperial College London in partnership with Public Health England (PHE), collaborating with Ajit Lalvani. Sunil Maharjan and Blessing Okai were affiliated to the NIHR HPRU in Respiratory Infections and both based at the National Infection Service, Public Health England during this work. The views expressed in the publication are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health, arms’ length bodies, other government departments.

Publisher Copyright:
© 2020

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • Immunogenicity
  • Influenza
  • Oil-in-water adjuvant
  • Oral fluid
  • Vaccine

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