Viral Shedding in Recipients of Live Attenuated Influenza Vaccine in the 2016-2017 and 2017-2018 Influenza Seasons in the United Kingdom

David Jackson, Max Pitcher, Chris Hudson, Nick Andrews, Jo Southern, Joanna Ellis, Katja Höschler, Richard Pebody, Paul J Turner, Elizabeth Miller, Maria Zambon, David Jackson, Max Pitcher, Chris Hudson, Nick Andrews, Jo Southern, Joanna Ellis, Katja Höschler, Richard Pebody, Paul J Turner, Elizabeth Miller, Maria Zambon

Abstract

Background: The (H1N1)pdm09 live attenuated influenza vaccine (LAIV) strain was changed for the 2017-2018 influenza season to improve viral fitness, following poor protection against (H1N1)pdm09 viruses in 2015-2016. We conducted LAIV virus shedding studies to assess the effect of this change.

Methods: Children aged 2-18 years were recruited to receive LAIV in the 2016-2017 (n = 641) and 2017-2018 (n = 362) influenza seasons. Viruses from nasal swabs taken 1, 3, and 6 days postvaccination were quantified by reverse-transcription polymerase chain reaction and area under the curve titers were determined. Presence and quantity of shedding were compared between strains and seasons with adjustment for age and prior LAIV (n = 436), inactivated seasonal vaccine (n = 100), or (H1N1)pdm09 vaccine (n = 166) receipt.

Results: (H1N1)pdm09 detection (positivity) in 2016-2017 and 2017-2018 (11.2% and 3.9%, respectively) was lower than that of H3N2 (19.7% and 18.7%, respectively) and B/Victoria (28.9% and 33.9%, respectively). (H1N1)pdm09 positivity was higher in 2016-2017 than 2017-2018 (P = .005), but within shedding-positive participants, the (H1N1)pdm09 titer increased in 2017-2018 (P = .02). H3N2 and influenza B titers were similar between seasons. Positivity declined with age, and prior vaccination reduced the likelihood of shedding influenza B but not (H1N1)pdm09.

Conclusions: The (H1N1)pdm09 titer increased in 2017-2018, indicating more efficient virus replication in shedding-positive children than the 2016-2017 strain, although overall positivity was reduced. Age and vaccination history require consideration when correlating virus shedding and protection.

Clinical trials registration: NCT02143882, NCT02866942, and NCT03104790.

Keywords: LAIV; influenza; vaccine effectiveness; virus shedding.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Study flowchart. Children aged 2–18 years, either influenza vaccine naive or with live attenuated influenza vaccination in at least 2 of the 3 previous years, were recruited during the 2016–2017 and 2017–2018 influenza seasons. Samples from participants from whom 3 swabs were received (taken on days 1, 3, and 6 postvaccination) were subjected to quantitative viral shedding analysis. Blood samples were only taken during the 2016–2017 season and used to determine serum antibody titers pre- and postvaccination. Abbreviation: LAIV, live attenuated influenza vaccination.
Figure 2.
Figure 2.
Analysis of viral shedding titers. The area under the curve titers (PFU/mL/day) of individual virus-positive samples were separated into 9 groups, ranging from the lowest (133 PFU/mL) to the highest observed titer for any subtype, on a 2-fold increasing scale. The percentage of samples in each group is shown as samples positive for H1 (A), H3 (B), B/Victoria (C), and B/Yamagata (D) from the 2016–2017 and 2017–2018 cohorts. Abbreviations: AUC, area under the curve; PFU, plaque-forming unit.
Figure 3.
Figure 3.
The effect of participant age on viral shedding. The figure shows the percentage of total samples analyzed that were positive for each subtype when stratified by age in the 2016–2017 and 2017–2018 cohorts.Abbreviations; B/Vic, B/Victoria; B/Yam, B/Yamagata; H1 and H3, haemagglutinin subtype.

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Source: PubMed

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