Virus-derived immunostimulatory RNA induces type I IFN-dependent antibodies and T-cell responses during vaccination

Devin G. Fisher; Gaia M. Coppock; Carolina B. López

doi:10.1016/j.vaccine.2018.05.100

Virus-derived immunostimulatory RNA induces type I IFN-dependent antibodies and T-cell responses during vaccination

Devin G. Fisher, Gaia M. Coppock, Carolina B. López

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Adjuvants potentiate and direct the type of immunity elicited during vaccination. However, there is a shortage of adjuvants that elicit robust type-1 immunity required for the control of intracellular pathogens, including viruses. RNA derived from Sendai virus defective viral genomes (DVGs) stimulates RIG-I-like receptor signaling leading to type-1 immunity during infection. Here, we investigated whether a 268nt DVG-derived oligonucleotide (DDO) functions as a strong type-1 immunity-inducing adjuvant during vaccination against influenza virus. We show that DDO induces robust IgG2c antibody production when used in an inactivated influenza A virus (IAV) vaccine. Additionally, DDO induces Th1 and CD8⁺ T-cell responses able to protect against heterosubtypic IAV challenge. Interestingly, DDO synergized with AddaVax and skewed the immune response towards type-1 immunity. The adjuvancy of DDO alone and in synergy with AddaVax was heavily dependent on type I interferon signaling. Our data support a critical role for type I interferon in the induction of type-1 immune responses during vaccination and demonstrate that DDO is a type-1 immunity orienting vaccine adjuvant that can be used alone or in synergy with other adjuvants.

Original language	English
Pages (from-to)	4039-4045
Number of pages	7
Journal	Vaccine
Volume	36
Issue number	28
DOIs	https://doi.org/10.1016/j.vaccine.2018.05.100
State	Published - Jun 27 2018

Keywords

Adjuvant
Defective viral genomes
Influenza vaccine
Type-1 immunity

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10.1016/j.vaccine.2018.05.100

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title = "Virus-derived immunostimulatory RNA induces type I IFN-dependent antibodies and T-cell responses during vaccination",

abstract = "Adjuvants potentiate and direct the type of immunity elicited during vaccination. However, there is a shortage of adjuvants that elicit robust type-1 immunity required for the control of intracellular pathogens, including viruses. RNA derived from Sendai virus defective viral genomes (DVGs) stimulates RIG-I-like receptor signaling leading to type-1 immunity during infection. Here, we investigated whether a 268nt DVG-derived oligonucleotide (DDO) functions as a strong type-1 immunity-inducing adjuvant during vaccination against influenza virus. We show that DDO induces robust IgG2c antibody production when used in an inactivated influenza A virus (IAV) vaccine. Additionally, DDO induces Th1 and CD8+ T-cell responses able to protect against heterosubtypic IAV challenge. Interestingly, DDO synergized with AddaVax and skewed the immune response towards type-1 immunity. The adjuvancy of DDO alone and in synergy with AddaVax was heavily dependent on type I interferon signaling. Our data support a critical role for type I interferon in the induction of type-1 immune responses during vaccination and demonstrate that DDO is a type-1 immunity orienting vaccine adjuvant that can be used alone or in synergy with other adjuvants.",

keywords = "Adjuvant, Defective viral genomes, Influenza vaccine, Type-1 immunity",

author = "Fisher, {Devin G.} and Coppock, {Gaia M.} and L{\'o}pez, {Carolina B.}",

note = "Funding Information: The authors wish to thank: Dr. Scott Hensley (University of Pennsylvania) for advising on virus challenge for IAV-Cal/09-D225G. We acknowledge the NIH Tetramer Core Facility (contract HHSN272201300006C) for provision of the IAV-NP tetramers. This work was supported by the US National Institutes of Health National Institute of Allergy and Infectious Diseases (NIH R01 AI083284 to C.B.L). Funding Information: The authors wish to thank: Dr. Scott Hensley ( University of Pennsylvania ) for advising on virus challenge for IAV-Cal/09-D225G . We acknowledge the NIH Tetramer Core Facility (contract HHSN272201300006C ) for provision of the IAV-NP tetramers. This work was supported by the US National Institutes of Health National Institute of Allergy and Infectious Diseases ( NIH R01 AI083284 to C.B.L ). Publisher Copyright: {\textcopyright} 2018",

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doi = "10.1016/j.vaccine.2018.05.100",

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AU - Coppock, Gaia M.

AU - López, Carolina B.

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N2 - Adjuvants potentiate and direct the type of immunity elicited during vaccination. However, there is a shortage of adjuvants that elicit robust type-1 immunity required for the control of intracellular pathogens, including viruses. RNA derived from Sendai virus defective viral genomes (DVGs) stimulates RIG-I-like receptor signaling leading to type-1 immunity during infection. Here, we investigated whether a 268nt DVG-derived oligonucleotide (DDO) functions as a strong type-1 immunity-inducing adjuvant during vaccination against influenza virus. We show that DDO induces robust IgG2c antibody production when used in an inactivated influenza A virus (IAV) vaccine. Additionally, DDO induces Th1 and CD8+ T-cell responses able to protect against heterosubtypic IAV challenge. Interestingly, DDO synergized with AddaVax and skewed the immune response towards type-1 immunity. The adjuvancy of DDO alone and in synergy with AddaVax was heavily dependent on type I interferon signaling. Our data support a critical role for type I interferon in the induction of type-1 immune responses during vaccination and demonstrate that DDO is a type-1 immunity orienting vaccine adjuvant that can be used alone or in synergy with other adjuvants.

AB - Adjuvants potentiate and direct the type of immunity elicited during vaccination. However, there is a shortage of adjuvants that elicit robust type-1 immunity required for the control of intracellular pathogens, including viruses. RNA derived from Sendai virus defective viral genomes (DVGs) stimulates RIG-I-like receptor signaling leading to type-1 immunity during infection. Here, we investigated whether a 268nt DVG-derived oligonucleotide (DDO) functions as a strong type-1 immunity-inducing adjuvant during vaccination against influenza virus. We show that DDO induces robust IgG2c antibody production when used in an inactivated influenza A virus (IAV) vaccine. Additionally, DDO induces Th1 and CD8+ T-cell responses able to protect against heterosubtypic IAV challenge. Interestingly, DDO synergized with AddaVax and skewed the immune response towards type-1 immunity. The adjuvancy of DDO alone and in synergy with AddaVax was heavily dependent on type I interferon signaling. Our data support a critical role for type I interferon in the induction of type-1 immune responses during vaccination and demonstrate that DDO is a type-1 immunity orienting vaccine adjuvant that can be used alone or in synergy with other adjuvants.

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SN - 0264-410X

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EP - 4045

JO - Vaccine

JF - Vaccine

IS - 28

ER -

Virus-derived immunostimulatory RNA induces type I IFN-dependent antibodies and T-cell responses during vaccination

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Keywords

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