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Volume 13
Issue 9
10.3390/v13091708
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Article

Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses

by
Nutan Mytle
1,2,†,
Sonja Leyrer
1,3,†,
Jon R. Inglefield
1,4,
Andrea M. Harris
1,
Thomas E. Hickey
1,5,
Jacob Minang
1,6,
Hang Lu
1,
Zhidong Ma
1,
Hanné Andersen
7,
Nathan D. Grubaugh
1,8,
Tina Guina
1,9,
Mario H. Skiadopoulos
1,10 and
Michael J. Lacy
1,*,†
1
Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA
2
Biomedical Advanced Research and Development Agency, U.S. Department of Health and Human Services, Washington, DC 20201, USA
3
Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany
4
Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
5
National Cancer Institute, National Institutes of Health, Frederick, MD 20814, USA
6
Optimal Health Care, 11377 Robinwood Dr, Hagerstown, MD 21742, USA
7
BIOQUAL, Inc., 12301 Parklawn Dr, Rockville, MD 20852, USA
8
Yale School of Public Health, Yale University, 60 College Street, New Haven, CT 06510, USA
9
AstraZeneca, Gaithersburg, MD 20878, USA
10
U.S. Department of Health and Human Services, National Institutes of Health, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editors: Marios Koutsakos and Sophie Valkenburg
Viruses 2021, 13(9), 1708; https://doi.org/10.3390/v13091708
Received: 9 July 2021 / Revised: 24 August 2021 / Accepted: 26 August 2021 / Published: 27 August 2021
(This article belongs to the Special Issue Immunity to Influenza Viruses)
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Abstract

Influenza hemagglutinin (HA) is considered a major protective antigen of seasonal influenza vaccine but antigenic drift of HA necessitates annual immunizations using new circulating HA versions. Low variation found within conserved non-HA influenza virus (INFV) antigens may maintain protection with less frequent immunizations. Conserved antigens of influenza A virus (INFV A) that can generate cross protection against multiple INFV strains were evaluated in BALB/c mice using modified Vaccinia virus Ankara (MVA)-vectored vaccines that expressed INFV A antigens hemagglutinin (HA), matrix protein 1 (M1), nucleoprotein (NP), matrix protein 2 (M2), repeats of the external portion of M2 (M2e) or as tandem repeats (METR), and M2e with transmembrane region and cytoplasmic loop (M2eTML). Protection by combinations of non-HA antigens was equivalent to that of subtype-matched HA. Combinations of NP and forms of M2e generated serum antibody responses and protected mice against lethal INFV A challenge using PR8, pandemic H1N1 A/Mexico/4108/2009 (pH1N1) or H5N1 A/Vietnam/1203/2004 (H5N1) viruses, as demonstrated by reduced lung viral burden and protection against weight loss. The highest levels of protection were obtained with NP and M2e antigens delivered as MVA inserts, resulting in broadly protective immunity in mice and enhancement of previous natural immunity to INFV A. View Full-Text
Keywords: modified Vaccinia virus Ankara (MVA); influenza A; nucleoprotein; matrix protein 1; matrix protein 2; hemagglutinin; conserved antigens; vaccine modified Vaccinia virus Ankara (MVA); influenza A; nucleoprotein; matrix protein 1; matrix protein 2; hemagglutinin; conserved antigens; vaccine
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MDPI and ACS Style

Mytle, N.; Leyrer, S.; Inglefield, J.R.; Harris, A.M.; Hickey, T.E.; Minang, J.; Lu, H.; Ma, Z.; Andersen, H.; Grubaugh, N.D.; Guina, T.; Skiadopoulos, M.H.; Lacy, M.J. Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses. Viruses 2021, 13, 1708. https://doi.org/10.3390/v13091708

AMA Style

Mytle N, Leyrer S, Inglefield JR, Harris AM, Hickey TE, Minang J, Lu H, Ma Z, Andersen H, Grubaugh ND, Guina T, Skiadopoulos MH, Lacy MJ. Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses. Viruses. 2021; 13(9):1708. https://doi.org/10.3390/v13091708

Chicago/Turabian Style

Mytle, Nutan, Sonja Leyrer, Jon R. Inglefield, Andrea M. Harris, Thomas E. Hickey, Jacob Minang, Hang Lu, Zhidong Ma, Hanné Andersen, Nathan D. Grubaugh, Tina Guina, Mario H. Skiadopoulos, and Michael J. Lacy. 2021. "Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses" Viruses 13, no. 9: 1708. https://doi.org/10.3390/v13091708

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