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

  1. Author:
    Mytle, Nutan
    Leyrer, Sonja
    Inglefield,Jon
    Harris, Andrea M
    Hickey,Thomas
    Minang, Jacob
    Lu, Hang
    Ma, Zhidong
    Andersen, Hanné
    Grubaugh, Nathan D
    Guina, Tina
    Skiadopoulos, Mario H
    Lacy, Michael J [ORCID]

  2. Author Address

    Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USA., Biomedical Advanced Research and Development Agency, U.S. Department of Health and Human Services, Washington, DC 20201, USA., Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., National Cancer Institute, National Institutes of Health, Frederick, MD 20814, USA., Optimal Health Care, 11377 Robinwood Dr, Hagerstown, MD 21742, USA., BIOQUAL, Inc., 12301 Parklawn Dr, Rockville, MD 20852, USA., Yale School of Public Health, Yale University, 60 College Street, New Haven, CT 06510, USA., AstraZeneca, Gaithersburg, MD 20878, USA., U.S. Department of Health and Human Services, National Institutes of Health, Bethesda, MD 20892, USA.,
    1. Year: 2021
    2. Date: Aug 27
    3. Epub Date: 2021 Aug 27
  2. Journal: Viruses
    1. 13
    2. 9
  4. Type of Article: Article
  5. Article Number: ARTN 1708
  6. ISSN: 1999-4915
  1. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.3390/v13091708
  3. PMID: 34578289
  4. PMCID: PMC8473317
  5. View record in Web of Science®
  6. WOS: 000702111400001
  7. PII : v13091708

Library Notes

  1. Fiscal Year: FY2020-2021
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