tetano
Editor, Senior Moderator
PLoS One. 2018 Apr 11;13(4):e0193680. doi: 10.1371/journal.pone.0193680. eCollection 2018.
[h=1]Broad cross-reactive IgG responses elicited by adjuvanted vaccination with recombinant influenza hemagglutinin (rHA) in ferrets and mice.[/h] Wang J[SUP]1[/SUP], Hilchey SP[SUP]1[/SUP], DeDiego M[SUP]2[/SUP], Perry S[SUP]1[/SUP], Hyrien O[SUP]3[/SUP], Nogales A[SUP]3[/SUP], Garigen J[SUP]1[/SUP], Amanat F[SUP]4[/SUP], Huertas N[SUP]4[/SUP], Krammer F[SUP]5[/SUP], Martinez-Sobrido L[SUP]3[/SUP], Topham DJ[SUP]3[/SUP], Treanor JJ[SUP]6[/SUP], Sangster MY[SUP]3[/SUP], Zand MS[SUP]1,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Annual immunization against influenza virus is a large international public health effort. Accumulating evidence suggests that antibody mediated cross-reactive immunity against influenza hemagglutinin (HA) strongly correlates with long-lasting cross-protection against influenza virus strains that differ from the primary infection or vaccination strain. However, the optimal strategies for achieving highly cross-reactive antibodies to the influenza virus HA have not yet to be defined. In the current study, using Luminex-based mPlex-Flu assay, developed by our laboratory, to quantitatively measure influenza specific IgG antibody mediated cross-reactivity, we found that prime-boost-boost vaccination of ferrets with rHA proteins admixed with adjuvant elicited higher magnitude and broader cross-reactive antibody responses than that induced by actual influenza viral infection, and this cross-reactive response likely correlated with increased anti-stalk reactive antibodies. We observed a similar phenomenon in mice receiving three sequential vaccinations with rHA proteins from either A/California/07/2009 (H1N1) or A/Hong Kong/1/1968 (H3N2) viruses admixed with Addavax, an MF59-like adjuvant. Using this same mouse vaccination model, we determined that Addavax plays a more significant role in the initial priming event than in subsequent boosts. We also characterized the generation of cross-reactive antibody secreting cells (ASCs) and memory B cells (MBCs) when comparing vaccination to viral infection. We have also found that adjuvant plays a critical role in the generation of long-lived ASCs and MBCs cross-reactive to influenza viruses as a result of vaccination with rHA of influenza virus, and the observed increase in stalk-reactive antibodies likely contributes to this IgG mediated broad cross-reactivity.
PMID: 29641537 DOI: 10.1371/journal.pone.0193680
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[h=1]Broad cross-reactive IgG responses elicited by adjuvanted vaccination with recombinant influenza hemagglutinin (rHA) in ferrets and mice.[/h] Wang J[SUP]1[/SUP], Hilchey SP[SUP]1[/SUP], DeDiego M[SUP]2[/SUP], Perry S[SUP]1[/SUP], Hyrien O[SUP]3[/SUP], Nogales A[SUP]3[/SUP], Garigen J[SUP]1[/SUP], Amanat F[SUP]4[/SUP], Huertas N[SUP]4[/SUP], Krammer F[SUP]5[/SUP], Martinez-Sobrido L[SUP]3[/SUP], Topham DJ[SUP]3[/SUP], Treanor JJ[SUP]6[/SUP], Sangster MY[SUP]3[/SUP], Zand MS[SUP]1,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Annual immunization against influenza virus is a large international public health effort. Accumulating evidence suggests that antibody mediated cross-reactive immunity against influenza hemagglutinin (HA) strongly correlates with long-lasting cross-protection against influenza virus strains that differ from the primary infection or vaccination strain. However, the optimal strategies for achieving highly cross-reactive antibodies to the influenza virus HA have not yet to be defined. In the current study, using Luminex-based mPlex-Flu assay, developed by our laboratory, to quantitatively measure influenza specific IgG antibody mediated cross-reactivity, we found that prime-boost-boost vaccination of ferrets with rHA proteins admixed with adjuvant elicited higher magnitude and broader cross-reactive antibody responses than that induced by actual influenza viral infection, and this cross-reactive response likely correlated with increased anti-stalk reactive antibodies. We observed a similar phenomenon in mice receiving three sequential vaccinations with rHA proteins from either A/California/07/2009 (H1N1) or A/Hong Kong/1/1968 (H3N2) viruses admixed with Addavax, an MF59-like adjuvant. Using this same mouse vaccination model, we determined that Addavax plays a more significant role in the initial priming event than in subsequent boosts. We also characterized the generation of cross-reactive antibody secreting cells (ASCs) and memory B cells (MBCs) when comparing vaccination to viral infection. We have also found that adjuvant plays a critical role in the generation of long-lived ASCs and MBCs cross-reactive to influenza viruses as a result of vaccination with rHA of influenza virus, and the observed increase in stalk-reactive antibodies likely contributes to this IgG mediated broad cross-reactivity.
PMID: 29641537 DOI: 10.1371/journal.pone.0193680
Free full text