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Master of Public Health

The effect of pre-existing immunity on virus detection and immune responses in a phase II randomized trial of a Russian-backbone live attenuated influenza vaccine in Bangladeshi children

AUTHORS

Brickley EB , Wright PF , Khalenkov A , Neuzil KM , Ortiz JR , Rudenko L , Levine MZ , Katz JM , Brooks WA , . Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018 11 27; ().

ABSTRACT

Background: In a 2012 phase II clinical trial (NCT01625689), 300 Bangladeshi children aged 24 to 59 months with no prior influenza vaccine exposure were randomized to receive a single dose of intra-nasally administered trivalent Russian-backbone live attenuated influenza vaccine (LAIV) or placebo. Protocol-defined analyses, presented in the companion manuscript, demonstrate decreased viral detection and immunogenicity for A/H1N1pdm09 relative to the A/H3N2 and B strains. This post-hoc analysis of the trial data aims to investigate the LAIV strain differences by testing the hypothesis that pre-existing immunity may influence viral recovery and immune responses after LAIV receipt.

Methods: We used logistic regressions to evaluate the relations between markers of pre-existing immunity (i.e., hemagglutination inhibition (HAI), microneutralization, and IgA and IgG antibodies) and LAIV viral recovery in the week post-vaccination. We then tested for potential effect modification by baseline HAI titers (i.e., <10 versus ≥10) and week 1 viral recovery on the LAIV-induced serum and mucosal immune responses measured between days 0 and 21 post-vaccination.

Results: Higher levels of pre-existing immunity to influenza A/H3N2 and B were strongly associated with strain-specific prevention of viral shedding upon LAIV receipt. While evidence of LAIV immunogenicity was observed for all three strains, the magnitudes of immune responses were most pronounced in children with no evidence of pre-existing HAI and in those with detectable virus.

Conclusion: The results provide evidence for a bidirectional association between viral replication and immunity and underscore the importance of accounting for pre-existing immunity when evaluating virologic and immunologic responses to LAIVs.

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