Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine
Abstract
:1. Introduction
2. Neuraminidase and Its Potential as a Vaccine Target
3. In Vitro and Animal Studies
4. Importance of NA Immunity in Humans
5. NA-Based Vaccine Strategies
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Subject | Neuraminidase Manufacturing Strategy | Outcome in NA-Vaccinated Subjects | Reference |
---|---|---|---|
White leghorn chickens | Electrophoresis-purified influenza A N2 | Increased NAI titers, decreased tracheal and cloacal viral titers | [64] |
Guinea pigs | Baculovirus expression system influenza B NA | NAI titers, increased ELISA antibody titers, decreased nasal wash virus titers, decreased transmission | [66] |
Manor Farm (MF-1) mice | Electrophoresis-purified influenza A N2 | Increased NAI titers, decreased pulmonary virus titers, diminished lung lesions | [57] |
BALB/c mice | Chromatography-purified influenza A N2 | Increased NAI titers, increased ELISA antibody titers, decreased weight loss, decreased pulmonary virus titers with homotypic and heterotypic challenge | [48,59,60,61,62,63,70] |
BALB/c mice | Baculovirus expression system influenza A N1, N2 and influenza B NA | Increased NAI titers, increased ELISA antibody titers, decreased pulmonary virus titers with homotypic and heterotypic challenge | [58,68,71,72,73,74,75] |
BALB/c mice | Yeast expression system influenza A N2 | Increased survival | [76] |
New Zealand rabbits | Chromatography-purified influenza A N2 | Increased NAI titers | [77,78] |
Ferrets | Human embryonic kidney cell expression system influenza A N1 | Increased NAI titers, decreased pulmonary virus titers, decreased lung pathology | [65] |
Humans | Chromatography-purified influenza A N2 | Increased NAI titers, increased ELISA antibody titers | [79] |
Vaccine Type | Vaccine Year | NA Activity (mU/mL) | NA Concentration (μg/mL) | Reference |
---|---|---|---|---|
Monovalent whole virus (H3N2) | 1968/1969 | 112,000 a | 43 | [118] |
Monovalent split virus (B) | 1973/1974 | 21,000 a | 165 | [118] |
Bivalent whole virus (H3N2 + B) | 1973/1974 | 78,000 a | 284 | [118] |
Bivalent whole virus (H3N2 + B) | 1974/1975 | 164,000–184,000 a | 372–692 | [118] |
Trivalent whole virus | 1975/1976 | 206,000 a | 596 | [118] |
Trivalent split virus | 1975/1976 | 50,000 a | 135 | [118] |
Bivalent whole virus (H3N2 + H1N1) | 1976/1977 | 10,400-60,000 a | 81–242 | [118] |
Monovalent whole virus (H1N1) | 1976/1977 | <500 a | 45–98 | [118] |
Monovalent (pH1N1) c | 2009 | - | 0.73–5.28 | [119] |
Monovalent (pH1N1) c | 2009 | 2–56 b | 9 | [16] |
Trivalent split virus | 2008/2009 | 194–3293 b | - | [16] |
Trivalent c | 2011/2012 | 2–3105 b | 22 | [16] |
Trivalent c | 2012/2013 | 4521 b | - | [16] |
Trivalent subunit (egg derived) | 2013/2014 | - | 5 | [120] |
Trivalent subunit (cell derived) | 2013/2014 | - | 0.02 | [120] |
Trivalent split virus (egg derived) | 2013/2014 | - | 10.5 | [120] |
Trivalent split virus (egg derived) | 2013/2014 | - | 4.4 | [120] |
Quadrivalent split virus (egg derived) | 2015/2016 | - | 2.7 | [127] |
Quadrivalent split virus (egg derived) | 2015/2016 | - | 3.9 | [127] |
Quadrivalent split virus high-dose (egg derived) | 2015/2016 | - | 12.9 | [127] |
Trivalent split virus (egg derived) | 2015/2016 | - | 2.4 | [127] |
Trivalent subunit (egg derived) | 2015/2016 | - | 3.4 | [127] |
Quadrivalent live-attenuated virus | 2015/2016 | - | 1.1 | [127] |
Quadrivalent split virus (egg derived) | 2016/2017 | - | 2.8 | [127] |
Quadrivalent split virus (egg derived) | 2016/2017 | - | 3.5 | [127] |
Quadrivalent split virus high-dose (egg derived) | 2016/2017 | - | 9.5 | [127] |
Trivalent split virus (egg derived) | 2016/2017 | - | 1.6 | [127] |
Trivalent subunit (egg derived) | 2016/2017 | - | 2.8 | [127] |
Quadrivalent live-attenuated virus | 2016/2017 | - | 0.4 | [127] |
Quadrivalent split virus (egg derived) | 2017/2018 | - | 2.0 | [127] |
Quadrivalent split virus (egg derived) | 2017/2018 | - | 3.2 | [127] |
Quadrivalent split virus high-dose (egg derived) | 2017/2018 | - | 7.9 | [127] |
Trivalent split virus (egg derived) | 2017/2018 | - | 1.5 | [127] |
Trivalent subunit (egg derived) | 2017/2018 | - | 3.1 | [127] |
Quadrivalent live-attenuated virus | 2017/2018 | - | 0.7 | [127] |
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Giurgea, L.T.; Morens, D.M.; Taubenberger, J.K.; Memoli, M.J. Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine. Vaccines 2020, 8, 409. https://doi.org/10.3390/vaccines8030409
Giurgea LT, Morens DM, Taubenberger JK, Memoli MJ. Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine. Vaccines. 2020; 8(3):409. https://doi.org/10.3390/vaccines8030409
Chicago/Turabian StyleGiurgea, Luca T., David M. Morens, Jeffery K. Taubenberger, and Matthew J. Memoli. 2020. "Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine" Vaccines 8, no. 3: 409. https://doi.org/10.3390/vaccines8030409
APA StyleGiurgea, L. T., Morens, D. M., Taubenberger, J. K., & Memoli, M. J. (2020). Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine. Vaccines, 8(3), 409. https://doi.org/10.3390/vaccines8030409