tetano
Editor, Senior Moderator
Cell Host Microbe. 2017 Mar 8;21(3):334-343. doi: 10.1016/j.chom.2017.02.007.
[h=1]Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets.[/h] Wang L[SUP]1[/SUP], Liu SY[SUP]2[/SUP], Chen HW[SUP]3[/SUP], Xu J[SUP]4[/SUP], Chapon M[SUP]2[/SUP], Zhang T[SUP]4[/SUP], Zhou F[SUP]5[/SUP], Wang YE[SUP]2[/SUP], Quanquin N[SUP]2[/SUP], Wang G[SUP]5[/SUP], Tian X[SUP]6[/SUP], He Z[SUP]7[/SUP], Liu L[SUP]7[/SUP], Yu W[SUP]7[/SUP], Sanchez DJ[SUP]8[/SUP], Liang Y[SUP]9[/SUP], Jiang T[SUP]4[/SUP], Modlin R[SUP]10[/SUP], Bloom BR[SUP]11[/SUP], Li Q[SUP]7[/SUP], Deng JC[SUP]6[/SUP], Zhou P[SUP]5[/SUP], Qin FX[SUP]12[/SUP], Cheng G[SUP]13[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD[SUB]50[/SUB] of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.
Copyright ? 2017 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] flu vaccine; genome-wide mutagenesis; influenza vaccine; matrix protein
PMID: 28279345 DOI: 10.1016/j.chom.2017.02.007
[h=1]Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets.[/h] Wang L[SUP]1[/SUP], Liu SY[SUP]2[/SUP], Chen HW[SUP]3[/SUP], Xu J[SUP]4[/SUP], Chapon M[SUP]2[/SUP], Zhang T[SUP]4[/SUP], Zhou F[SUP]5[/SUP], Wang YE[SUP]2[/SUP], Quanquin N[SUP]2[/SUP], Wang G[SUP]5[/SUP], Tian X[SUP]6[/SUP], He Z[SUP]7[/SUP], Liu L[SUP]7[/SUP], Yu W[SUP]7[/SUP], Sanchez DJ[SUP]8[/SUP], Liang Y[SUP]9[/SUP], Jiang T[SUP]4[/SUP], Modlin R[SUP]10[/SUP], Bloom BR[SUP]11[/SUP], Li Q[SUP]7[/SUP], Deng JC[SUP]6[/SUP], Zhou P[SUP]5[/SUP], Qin FX[SUP]12[/SUP], Cheng G[SUP]13[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD[SUB]50[/SUB] of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.
Copyright ? 2017 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] flu vaccine; genome-wide mutagenesis; influenza vaccine; matrix protein
PMID: 28279345 DOI: 10.1016/j.chom.2017.02.007