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Single-replication BM2SR vaccine provides sterilizing immunity and cross-lineage influenza B virus protection in mice

tetano

Editor, Senior Moderator
Vaccine. 2019 Jul 4. pii: S0264-410X(19)30805-9. doi: 10.1016/j.vaccine.2019.06.043. [Epub ahead of print]
[h=1]Single-replication BM2SR vaccine provides sterilizing immunity and cross-lineage influenza B virus protection in mice.[/h] Moser MJ[SUP]1[/SUP], Hatta Y[SUP]1[/SUP], Gabaglia C[SUP]2[/SUP], Sanchez A[SUP]2[/SUP], Dias P[SUP]2[/SUP], Sarawar S[SUP]2[/SUP], Kawaoka Y[SUP]3[/SUP], Hatta M[SUP]4[/SUP], Neumann G[SUP]4[/SUP], Bilsel P[SUP]5[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Both influenza A and B viruses cause outbreaks of seasonal influenza resulting in significant morbidity and mortality. There are two antigenically distinct lineages of influenza B virus, Yamagata lineage (YL) and Victoria lineage (VL). Since both B lineages have been co-circulating for years, more than 70% of influenza vaccines currently manufactured are quadrivalent consisting of influenza A (H1N1), influenza A (H3N2), influenza B (YL) and influenza B (VL) antigens. Although quadrivalent influenza vaccines tend to elevate immunity to both influenza B lineages, estimated overall vaccine efficacy against influenza B is still only around 42%. Thus, a more effective influenza B vaccine is needed. To meet this need, we generated BM2-deficient, single-replication (BM2SR) influenza B vaccine viruses that encode surface antigens from influenza B/Wisconsin/01/2010 (B/WI01, YL) and B/Brisbane/60/2008 (B/Bris60, VL) viruses. The BM2SR-WI01 and BM2SR-Bris60 vaccine viruses are replication-deficient in vitro and in vivo, and can only replicate in a cell line that expresses the complementing BM2 protein. Both BM2SR viruses were non-pathogenic to mice, and vaccinated animals showed elevated mucosal and serum antibody responses to both Yamagata and Victoria lineages in addition to cellular responses. Serum antibody responses included lineage-specific hemagglutinin inhibition antibody (HAI) responses as well as responses to the stem region of the hemagglutinin (HA). BM2SR vaccine viruses provided apparent sterilizing immunity to mice against intra- and inter-lineage drifted B virus challenge. The data presented here support the feasibility of BM2SR as a platform for next-generation trivalent influenza vaccine development.
Copyright ? 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.


[h=4]KEYWORDS:[/h] BM2-deficient; Cross-lineage protection; Drifted; Hemagglutination inhibition; Influenza B; Influenza vaccine; Intranasal; Live influenza; Single replication

PMID: 31280945 DOI: 10.1016/j.vaccine.2019.06.043
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