Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses
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...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/9/1708 |
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| author | Nutan Mytle 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 Michael J. Lacy |
| author_facet | Nutan Mytle 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 Michael J. Lacy |
| author_sort | Nutan Mytle |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T07:08:18Z |
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| id | doaj.art-0e2b6e7f55d14878899c653faf728f7d |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T07:08:18Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-0e2b6e7f55d14878899c653faf728f7d2023-11-22T15:36:47ZengMDPI AGViruses1999-49152021-08-01139170810.3390/v13091708Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A VirusesNutan Mytle0Sonja Leyrer1Jon R. Inglefield2Andrea M. Harris3Thomas E. Hickey4Jacob Minang5Hang Lu6Zhidong Ma7Hanné Andersen8Nathan D. Grubaugh9Tina Guina10Mario H. Skiadopoulos11Michael J. Lacy12Emergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USABIOQUAL, Inc., 12301 Parklawn Dr, Rockville, MD 20852, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAEmergent BioSolutions, 300 Professional Drive, Gaithersburg, MD 20879, USAInfluenza 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.https://www.mdpi.com/1999-4915/13/9/1708modified Vaccinia virus Ankara (MVA)influenza Anucleoproteinmatrix protein 1matrix protein 2hemagglutinin |
| spellingShingle | Nutan Mytle 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 Michael J. Lacy 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 modified Vaccinia virus Ankara (MVA) influenza A nucleoprotein matrix protein 1 matrix protein 2 hemagglutinin |
| title | Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses |
| title_full | Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses |
| title_fullStr | Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses |
| title_full_unstemmed | Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses |
| title_short | Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses |
| title_sort | influenza antigens np and m2 confer cross protection to balb c mice against lethal challenge with h1n1 pandemic h1n1 or h5n1 influenza a viruses |
| topic | modified Vaccinia virus Ankara (MVA) influenza A nucleoprotein matrix protein 1 matrix protein 2 hemagglutinin |
| url | https://www.mdpi.com/1999-4915/13/9/1708 |
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