Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice
ABSTRACT In an attempt to assess the cross-protective potential of the influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to lethal challenge with homologous, heterologous, or heterosub...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2015-05-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02556-14 |
| _version_ | 1818892643123331072 |
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| author | Teddy John Wohlbold Raffael Nachbagauer Haoming Xu Gene S. Tan Ariana Hirsh Karl A. Brokstad Rebecca J. Cox Peter Palese Florian Krammer |
| author_facet | Teddy John Wohlbold Raffael Nachbagauer Haoming Xu Gene S. Tan Ariana Hirsh Karl A. Brokstad Rebecca J. Cox Peter Palese Florian Krammer |
| author_sort | Teddy John Wohlbold |
| collection | DOAJ |
| description | ABSTRACT In an attempt to assess the cross-protective potential of the influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to lethal challenge with homologous, heterologous, or heterosubtypic viruses. Mice immunized with NA of subtype N2 were completely protected from morbidity and mortality in a homologous challenge and displayed significantly reduced viral lung titers. Heterologous challenge with a drifted strain resulted in morbidity but no mortality. Similar results were obtained for challenge experiments with N1 NA. Mice immunized with influenza B virus NA (from B/Yamagata/16/88) displayed no morbidity when sublethally infected with the homologous strain and, importantly, were completely protected from morbidity and mortality when lethally challenged with the prototype Victoria lineage strain or a more recent Victoria lineage isolate. Upon analyzing the NA content in 4 different inactivated-virus vaccine formulations from the 2013-2014 season via Western blot assay and enzyme-linked immunosorbent assay quantification, we found that the amount of NA does indeed vary across vaccine brands. We also measured hemagglutinin (HA) and NA endpoint titers in pre- and postvaccination human serum samples from individuals who received a trivalent inactivated seasonal influenza vaccine from the 2004-2005 season; the induction of NA titers was statistically less pronounced than the induction of HA titers. The demonstrated homologous and heterologous protective capacity of recombinant NA suggests that supplementing vaccine formulations with a standard amount of NA may offer increased protection against influenza virus infection. IMPORTANCE Despite the existence of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to cause morbidity and mortality in the human population, emphasizing the continued need for research in the field. While the majority of influenza vaccine strategies target the viral hemagglutinin, the immunodominant antigen on the surface of the influenza virion, antibodies against the viral neuraminidase (NA) have been correlated with less severe disease and decreased viral shedding in humans. Nevertheless, the amount of NA is not standardized in current seasonal vaccines, and the exact breadth of NA-based protection is unknown. Greater insight into the cross-protective potential of influenza virus NA as a vaccine antigen may pave the way for the development of influenza vaccines of greater breadth and efficacy. |
| first_indexed | 2024-12-19T17:59:58Z |
| format | Article |
| id | doaj.art-da8a80e009fe433e962da33989dcbe5a |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T17:59:58Z |
| publishDate | 2015-05-01 |
| publisher | American Society for Microbiology |
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| series | mBio |
| spelling | doaj.art-da8a80e009fe433e962da33989dcbe5a2022-12-21T20:11:42ZengAmerican Society for MicrobiologymBio2150-75112015-05-016210.1128/mBio.02556-14Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in MiceTeddy John Wohlbold0Raffael Nachbagauer1Haoming Xu2Gene S. Tan3Ariana Hirsh4Karl A. Brokstad5Rebecca J. Cox6Peter Palese7Florian Krammer8Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USABroegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, NorwayThe Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USAABSTRACT In an attempt to assess the cross-protective potential of the influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to lethal challenge with homologous, heterologous, or heterosubtypic viruses. Mice immunized with NA of subtype N2 were completely protected from morbidity and mortality in a homologous challenge and displayed significantly reduced viral lung titers. Heterologous challenge with a drifted strain resulted in morbidity but no mortality. Similar results were obtained for challenge experiments with N1 NA. Mice immunized with influenza B virus NA (from B/Yamagata/16/88) displayed no morbidity when sublethally infected with the homologous strain and, importantly, were completely protected from morbidity and mortality when lethally challenged with the prototype Victoria lineage strain or a more recent Victoria lineage isolate. Upon analyzing the NA content in 4 different inactivated-virus vaccine formulations from the 2013-2014 season via Western blot assay and enzyme-linked immunosorbent assay quantification, we found that the amount of NA does indeed vary across vaccine brands. We also measured hemagglutinin (HA) and NA endpoint titers in pre- and postvaccination human serum samples from individuals who received a trivalent inactivated seasonal influenza vaccine from the 2004-2005 season; the induction of NA titers was statistically less pronounced than the induction of HA titers. The demonstrated homologous and heterologous protective capacity of recombinant NA suggests that supplementing vaccine formulations with a standard amount of NA may offer increased protection against influenza virus infection. IMPORTANCE Despite the existence of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to cause morbidity and mortality in the human population, emphasizing the continued need for research in the field. While the majority of influenza vaccine strategies target the viral hemagglutinin, the immunodominant antigen on the surface of the influenza virion, antibodies against the viral neuraminidase (NA) have been correlated with less severe disease and decreased viral shedding in humans. Nevertheless, the amount of NA is not standardized in current seasonal vaccines, and the exact breadth of NA-based protection is unknown. Greater insight into the cross-protective potential of influenza virus NA as a vaccine antigen may pave the way for the development of influenza vaccines of greater breadth and efficacy.https://journals.asm.org/doi/10.1128/mBio.02556-14 |
| spellingShingle | Teddy John Wohlbold Raffael Nachbagauer Haoming Xu Gene S. Tan Ariana Hirsh Karl A. Brokstad Rebecca J. Cox Peter Palese Florian Krammer Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice mBio |
| title | Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice |
| title_full | Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice |
| title_fullStr | Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice |
| title_full_unstemmed | Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice |
| title_short | Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice |
| title_sort | vaccination with adjuvanted recombinant neuraminidase induces broad heterologous but not heterosubtypic cross protection against influenza virus infection in mice |
| url | https://journals.asm.org/doi/10.1128/mBio.02556-14 |
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