Responses to live attenuated influenza vaccine in children vaccinated previously with Pandemrix (ASO3B adjuvanted pandemic A/H1N1pdm09)

Katja Hoschler*, Joanna Southern, Catherine Thompson, Fiona Warburton, Nicholas Andrews, Elizabeth Miller, Maria Zambon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Background: We report a phase III/IV open-label study on the immunogenicity of a single dose of a Live Attenuated Influenza Vaccine (LAIV) (Fluenz™) in children naïve to, or in previous receipt of, AS03B adjuvanted A/H1N1pdm09 influenza vaccine (Pandemrix™), to investigate whether early exposure to an adjuvanted subunit influenza vaccine impacts on subsequent response to quadrivalent LAIV (qLAIV). Method and findings: Eligible children were enrolled to receive qLAIV and stratified according to previous Pandemrix™ vaccination. Functional antibody for the vaccine strains were analysed using Haemagglutination Inhibition (HAI); in addition antibodies to the A/H1N1pdm09 strain were measured by Neuraminidase Antibody Inhibition (NAI) and neutralisation assays. Fourfold titre increases by HAI were observed for 39% (95% confidence interval 33–46%) and 43% (37–51%) of subjects for the two influenza B vaccine strains and 8% (5–13%) for the A/H3N2 strain with no significant differences between the Pandemrix™ naïve or previously vaccinated groups in antibody tites pre- or post-vaccination or seroconversion rates. In both groups, the response to the qLAIV A/H1N1pdm09 component was barely detectable, overall HAI seroconversion rate 1.8% (0.5–4.7%). Previous receipt of Pandemrix™ was associated with significantly higher levels of A/H1N1pdm09 neutralising antibody, but decreased NAI titres pre-vaccination, with the differences maintained post-vaccination. Conclusion: Previous receipt of Pandemrix™ has had a significant impact on the influenza immune status of children several years later. Higher levels of neutralising antibody to A/H1N1pdm09 pre- and post-vaccination, but significantly lower levels of antibody to NA, were observed compared with Pandemrix™-naïve children, while responses to influenza B and A/H3N2 and antibody levels prior to vaccination were similar in both groups. This suggests that early vaccination with a powerful adjuvant maintains functional immunity for several years, which prevents natural infection. Alternatively, the AS03B adjuvant may have re-directed the immune response, with focus towards viral HA and away from viral NA.

Original languageEnglish
Pages (from-to)3034-3040
Number of pages7
JournalVaccine
Volume36
Issue number21
DOIs
Publication statusPublished - 17 May 2018

Bibliographical note

Funding Information:
This work was funded by the NIHR Policy Research Programme (National Vaccine Evaluation Consortium, Grant number 039/0031- grant holder EM). 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.

Funding Information:
The report is based on independent research commissioned and funded by the NIHR Policy Research Programme ( National Vaccine Evaluation Consortium , Grant number 039/0031 ). We thank Janice Baldevarona, Christine Carr, Sammy Ho, Monali Patel, Max Pitcher for their technical support at the Respiratory Virus Unit (PHE NIS, Colindale). We thank the Vaccine Research Nurses in Hertfordshire and Gloucestershire for the recruitment and follow up of the study participants, Mrs Pauline Kaye for database design and data management and staff in the Immunisation Department for study administration and data entry.

Keywords

  • Childhood
  • Cross-reactive effects
  • Influenza
  • Oil-in-water adjuvant
  • Vaccine

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