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Successes and failures of the live-attenuated influenza vaccine: can we do better?

tetano

Editor, Senior Moderator
Clin Infect Dis. 2019 May 6. pii: ciz358. doi: 10.1093/cid/ciz358. [Epub ahead of print]
[h=1]Successes and failures of the live-attenuated influenza vaccine: can we do better?[/h] Matrajt L[SUP]1[/SUP], Halloran ME[SUP]1,[/SUP][SUP]2[/SUP], Antia R[SUP]3[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] The effectiveness of the live attenuated influenza vaccine (LAIV) can vary widely, ranging from 0 - 50%. The reasons for these discrepancies remain largely unclear.
[h=4]METHODS:[/h] We use mathematical models to explore how the efficacy of LAIV is affected by the degree of mismatch with the currently circulating influenza strain and interference with pre-existing immunity. The models incorporate three key antigenic distances: the distances between the vaccine strain, pre-existing immunity, and the challenge strain.
[h=4]RESULTS:[/h] Our models show that a LAIV that is matched with the currently circulating strain is likely to have only modest efficacy. Our results suggest that the efficacy of the vaccine would be increased (optimized) if, rather than being matched to the circulating strain, it is antigenically slightly further from pre-existing immunity compared with the circulating strain. The models also suggest two regimes in which LAIV that is matched to circulating strains may be protective: in children before they have built immunity to circulating strains, and in response to novel strains (such as antigenic shifts) which are at substantial antigenic distance from previously circulating strains. We provide an explanation for the variation in vaccine effectiveness between studies and countries of vaccine effectiveness observed during the 2014-15 influenza season.
[h=4]CONCLUSIONS:[/h] LAIV is offered to children across the world, however, its effectiveness significantly varies between studies. Here, we propose a mechanistic explanation to understand these differences. We further propose a way to select the LAIV strain that would have a higher chance of being protective.
? The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.


[h=4]KEYWORDS:[/h] Live-attenuated influenza vaccine (LAIV); influenza; mathematical model; vaccine

PMID: 31056675 DOI: 10.1093/cid/ciz358
 
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