Enhanced immunogenicity following miR-155 incorporation into the influenza A virus genome

Leonard Izzard; Daniel Dlugolenski; Yingju Xia; Meagan McMahon; Deborah Middleton; Ralph A. Tripp; John Stambas

doi:10.1016/j.virusres.2017.04.002

Enhanced immunogenicity following miR-155 incorporation into the influenza A virus genome

Leonard Izzard, Daniel Dlugolenski, Yingju Xia, Meagan McMahon, Deborah Middleton, Ralph A. Tripp, John Stambas

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Abstract

Influenza A vaccine efficacy in the elderly is generally poor and so identification of novel molecular adjuvants to improve immunogenicity is important to reduce the overall burden of disease. Short non-coding RNAs, known as microRNAs (miRNAs) are known to regulate gene expression and have the potential to influence immune responses. One such miRNA, miR-155, has been shown to modulate T and B cell development and function. We incorporated miR-155 into the influenza A virus (IAV) genome creating a self-adjuvanting ‘live vaccine’ with the ability to modify immunogenicity. Infection of mice with a recombinant influenza virus encoding miR-155 in the NS gene segment altered epitope-specific expansion of influenza-specific CD8⁺ T cells and induced significantly higher levels of neutralising antibody.

Original language	English
Pages (from-to)	115-120
Number of pages	6
Journal	Virus Research
Volume	235
DOIs	https://doi.org/10.1016/j.virusres.2017.04.002
Publication status	Published - 2 May 2017
Externally published	Yes

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ArticleFinal published version, 529 KBLicence: CC BY-NC-ND

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title = "Enhanced immunogenicity following miR-155 incorporation into the influenza A virus genome",

abstract = "Influenza A vaccine efficacy in the elderly is generally poor and so identification of novel molecular adjuvants to improve immunogenicity is important to reduce the overall burden of disease. Short non-coding RNAs, known as microRNAs (miRNAs) are known to regulate gene expression and have the potential to influence immune responses. One such miRNA, miR-155, has been shown to modulate T and B cell development and function. We incorporated miR-155 into the influenza A virus (IAV) genome creating a self-adjuvanting {\textquoteleft}live vaccine{\textquoteright} with the ability to modify immunogenicity. Infection of mice with a recombinant influenza virus encoding miR-155 in the NS gene segment altered epitope-specific expansion of influenza-specific CD8+ T cells and induced significantly higher levels of neutralising antibody.",

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author = "Leonard Izzard and Daniel Dlugolenski and Yingju Xia and Meagan McMahon and Deborah Middleton and Tripp, {Ralph A.} and John Stambas",

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T1 - Enhanced immunogenicity following miR-155 incorporation into the influenza A virus genome

AU - Izzard, Leonard

AU - Dlugolenski, Daniel

AU - Xia, Yingju

AU - McMahon, Meagan

AU - Middleton, Deborah

AU - Tripp, Ralph A.

AU - Stambas, John

PY - 2017/5/2

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N2 - Influenza A vaccine efficacy in the elderly is generally poor and so identification of novel molecular adjuvants to improve immunogenicity is important to reduce the overall burden of disease. Short non-coding RNAs, known as microRNAs (miRNAs) are known to regulate gene expression and have the potential to influence immune responses. One such miRNA, miR-155, has been shown to modulate T and B cell development and function. We incorporated miR-155 into the influenza A virus (IAV) genome creating a self-adjuvanting ‘live vaccine’ with the ability to modify immunogenicity. Infection of mice with a recombinant influenza virus encoding miR-155 in the NS gene segment altered epitope-specific expansion of influenza-specific CD8+ T cells and induced significantly higher levels of neutralising antibody.

AB - Influenza A vaccine efficacy in the elderly is generally poor and so identification of novel molecular adjuvants to improve immunogenicity is important to reduce the overall burden of disease. Short non-coding RNAs, known as microRNAs (miRNAs) are known to regulate gene expression and have the potential to influence immune responses. One such miRNA, miR-155, has been shown to modulate T and B cell development and function. We incorporated miR-155 into the influenza A virus (IAV) genome creating a self-adjuvanting ‘live vaccine’ with the ability to modify immunogenicity. Infection of mice with a recombinant influenza virus encoding miR-155 in the NS gene segment altered epitope-specific expansion of influenza-specific CD8+ T cells and induced significantly higher levels of neutralising antibody.

KW - B cell

KW - Influenza A

KW - miR-155

KW - RNAi

KW - T cell

KW - Vaccine

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VL - 235

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JO - Virus Research

JF - Virus Research

ER -

Enhanced immunogenicity following miR-155 incorporation into the influenza A virus genome

Abstract

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