Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies

Norbert Pardi; Kaela Parkhouse; Ericka Kirkpatrick; Meagan McMahon; Seth J. Zost; Barbara L. Mui; Ying K. Tam; Katalin Karikó; Christopher J. Barbosa; Thomas D. Madden; Michael J. Hope; Florian Krammer; Scott E. Hensley; Drew Weissman

doi:10.1038/s41467-018-05482-0

Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies

Norbert Pardi, Kaela Parkhouse, Ericka Kirkpatrick, Meagan McMahon, Seth J. Zost, Barbara L. Mui, Ying K. Tam, Katalin Karikó, Christopher J. Barbosa, Thomas D. Madden, Michael J. Hope, Florian Krammer, Scott E. Hensley, Drew Weissman

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

220 Scopus citations

Abstract

Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.

Original language	English
Article number	3361
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-05482-0
State	Published - 1 Dec 2018

Access to Document

10.1038/s41467-018-05482-0

Cite this

Pardi, N., Parkhouse, K., Kirkpatrick, E., McMahon, M., Zost, S. J., Mui, B. L., Tam, Y. K., Karikó, K., Barbosa, C. J., Madden, T. D., Hope, M. J., Krammer, F., Hensley, S. E., & Weissman, D. (2018). Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. Nature Communications, 9(1), Article 3361. https://doi.org/10.1038/s41467-018-05482-0

@article{18c630f68ab9432cbece41e9fef82551,

title = "Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies",

abstract = "Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.",

author = "Norbert Pardi and Kaela Parkhouse and Ericka Kirkpatrick and Meagan McMahon and Zost, {Seth J.} and Mui, {Barbara L.} and Tam, {Ying K.} and Katalin Karik{\'o} and Barbosa, {Christopher J.} and Madden, {Thomas D.} and Hope, {Michael J.} and Florian Krammer and Hensley, {Scott E.} and Drew Weissman",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-05482-0",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies

AU - Pardi, Norbert

AU - Parkhouse, Kaela

AU - Kirkpatrick, Ericka

AU - McMahon, Meagan

AU - Zost, Seth J.

AU - Mui, Barbara L.

AU - Tam, Ying K.

AU - Karikó, Katalin

AU - Barbosa, Christopher J.

AU - Madden, Thomas D.

AU - Hope, Michael J.

AU - Krammer, Florian

AU - Hensley, Scott E.

AU - Weissman, Drew

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.

AB - Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.

UR - http://www.scopus.com/inward/record.url?scp=85052075576&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-05482-0

DO - 10.1038/s41467-018-05482-0

M3 - Article

C2 - 30135514

AN - SCOPUS:85052075576

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3361

ER -

Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies

Abstract

Access to Document

Fingerprint

Cite this