An Overview of Influenza Viruses and Vaccines
Abstract
:1. The Influenza Virus and Subtypes
2. Influenza Virus Life Cycle
- (1)
- Virus attachment to the sialic acid receptor: the first stage of viral infection is the attachment of HA to the sialic acids located at the host cell membrane’s surface. Sialic acids are connected to the carbohydrates of HA via glycosidic linkage. There are two linkages which are essential for the specificity of HA; (i) α (2, 3) linkage which is abundant in the digestive tract in avian or in the bronchial tissue in human, monkeys, horses, as well as upper respiratory tract of the lung epithelium in swine, and (ii) α (2, 6) which is found on the cell surface of the human upper respiratory tract as well as the trachea of bats and swine [4,18].
- (2)
- Entry of the virus into the host cell: receptor-mediated endocytosis occurs upon virus binding, and the virus enters the host cell in an endosome.
- (3)
- Fusion and uncoating of the virus particles: The acidic pH of the endosome (pH 5–6) causes the fusion of the viral and endosomal membranes and opens up the M2 ion channel protein and acidifies the nucleus, thus allowing vRNP to be released from M1 to enter the host cell’s cytoplasm and then to the nucleus.
- (4)
- vRNPs entry into the nucleus followed by transcription and replication: the viral proteins that constitute the vRNP (NP, PA, PB1, and PB2) detect the nuclear localization signals which can attach to the cellular nuclear import machinery and consequently, enter the nucleus to undergo the transcription and replication processes. The negative-sense RNA is first transformed into a positive-sense RNA and serves as a template for the generation of viral RNA, followed by the internal RNA synthesis initiated by the viral RNA-dependent RNA polymerase (RdRp). Through its C-terminal domain, the RdRp associates with the large subunit of RNA Polymerase II (Pol II), which continue the transcription to produce mature mRNA. vRNPs are then exported out from the viral core through the nuclear pores [19,20].
- (5)
- The assembly of virus components and budding: the virus’ protein components, i.e., HA, NA, and M2, are transported to the membrane’s apical region where the virions bud from the polarized epithelial cells.
- (6)
- The release of new virions from the host cells: after forming viral particles, the sialic acid residues from glycoproteins and glycolipids are cleaved by NA, enabling the newly synthesized viral particles to be released from the host membrane and spread to the nearby cells [21].
3. HA and NA of Influenza Virus
4. Glycosylation of HA and NA
5. The Influenza Epidemic vs. Pandemic
6. Vaccines against Influenza Epidemic and Pandemic
6.1. Inactivated Influenza Vaccine (IIV)
6.1.1. Whole-Virus Inactivated Vaccines (WIV)
6.1.2. Split-Virus Inactivated Vaccines
6.1.3. Subunit Inactivated Vaccines
6.2. Live Attenuated Influenza Vaccines (LAIV)
6.3. Recombinant HA Vaccine
7. Influenza Vaccine Manufacturing Processes
7.1. Egg-Based Vaccines
7.2. Cell-Based Vaccines
8. Influenza Vaccine Formulation and Ingredients
8.1. Active Components
8.2. Adjuvants
8.3. Stabilizers
8.4. Preservatives
8.5. Trace Components
9. Novel Influenza Vaccine Platforms
9.1. Virus-Like Particle (VLP) Vaccines
9.2. Antigen-Presenting Cell (APC) Inducible Vaccines
9.3. Nanoparticle-Based Influenza Vaccines
9.4. Universal Influenza Vaccines
10. Characterization of Vaccine Products
10.1. Purity
10.2. Quantity
10.3. Homogeneity
10.4. Stability
11. Effectiveness of Influenza Vaccines
12. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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No | Tradename | Manufacturer | Age Group | Country | References |
---|---|---|---|---|---|
Inactivated Influenza Vaccine, Split Virion, Egg-Based | |||||
1 | Afluria Quadrivalent | Seqirus Pty. Ltd. | Six months and over | US | [72] |
2 | Fluarix Quadrivalent | GlaxoSmithKline Biologicals | Six months and over | US | [73] |
3 | FluLaval Quadrivalent | ID Biomedical Corporation of Quebec | Six months and over | US | [74] |
4 | Fluzone Highdose Quadrivalent | Sanofi Pasteur, Inc. | 65 years and over | US | [75] |
5 | Fluzone Quadrivalent | Sanofi Pasteur, Inc. | Six months and over | US | [76] |
6 | FluQuadri | Sanofi-Aventis Australia | Six months and over | Australia | [77] |
7 | Vaxigrip Tetra | Sanofi-Aventis Australia | Six months and over | Australia | [78] |
8 | Fluarix Tetra | GlaxoSmithKline Biologicals | Six months and over | Australia | [74] |
9 | Afluria Quadrivalent | Seqirus Pty. Ltd. | Five years and over | Australia | [79] |
10 | Influvac Tetra | Mylan Health | Three years and over | Australia | [79] |
Inactivated Influenza Vaccine, Surface Antigen, Adjuvanted, Egg-Based | |||||
11 | Fluad | Seqirus, Inc. | 65 years and over | US | [80] |
12 | Fluad Quadrivalent | Seqirus, Inc. | 65 years and over | US | [81] |
13 | Fluad Quad | Seqirus, Inc. | 65 years and over | Australia | [80] |
Recombinant Vaccine | |||||
14 | Flublok Quadrivalent | Sanofi Pasteur, Inc. | 18 years and over | US | [82] |
Inactivated Subunit Influenza Vaccine, Cell Culture-Based | |||||
15 | Flucelvax Quadrivalent | Seqirus, Inc. | Four years and over | US | [83] |
Live Attenuated Influenza Vaccine | |||||
16 | FluMist Quadrivalent | MedImmune, LLC | Two years through 49 years | US | [84] |
VLP Vaccine Candidate | Type of Response | Cross-Protection | Clinical Phase | Type of Species | Sponsor | References |
---|---|---|---|---|---|---|
BV VLP-HA-NA-M1 | Humoral and cellular | N/A | Preclinical | Mice | - | [132] |
HBc VLP-M2e-HA2 (Tandiflu1) | Cellular | Yes | Preclinical | Mice | - | [133] |
HBc VLP-M2e-NP | Humoral and cellular | Yes | Preclinical | Mice | - | [127] |
Influenza VLP-HA (H1, H8, H13, H3, H4, H10) | Humoral | Yes | Preclinical | Mice | - | [134] |
Recombinant A (H1N1) 2009 influenza VLP vaccine (HA) | Humoral | N/A | Phase II | Human | Novavax | [135] |
HA and M2e5x | Humoral and cellular | N/A | Preclinical | Mice | - | [136] |
Plant-based QVLP (HA) | Humoral and cellular | Yes | Phase I &II | Human | Medicago | [131,137] |
Vaccine Candidate | Vaccine Type | Manufacturer | Clinical Phase | Participants | Mechanism of Action |
---|---|---|---|---|---|
Chimeric HA proteins [151] | Hemagglutinin based | Glaxo-SmithKline | Phase I | 66 | Ag-specific cellular response Broadly cross-reactive Abs |
Computationally optimized broadly reactive antigens (COBRA) [152] | Computationally optimized antigens | Sanofi-Pasteur | Preclinical | - | Elicitation of a unique broad cross-reactive and cross-neutralizing Ab against HA. |
NP, M1 and HA peptides (Multimeric-001) [153] | Recombinant proteins | BiondVax Pharmaceuticals Ltd./NIAID | Phase III | 12463 | Cellular (B- and T-cell) immune response. |
Assay or Technique | Use | References |
---|---|---|
Identity | ||
Hemagglutinin inhibition assay (HI Test) | Selection of the candidate virus vaccine CVV and stability | [158,159,160] |
Single radial immunodiffusion assay SRID | Vaccine potency | [161,162,163] |
Enzyme-linked immunosorbent assay ELISA | ||
Sedimentation | ||
Velocity | Mass and size | [164] |
Equilibrium | Mass, association | [164] |
Chromatography | ||
Hydrophobic interaction | Purification | [165] |
Reverse phase | Purification and stability | [166] |
Ion exchange | Charge | [167] |
Size exclusion | Size | [168] |
Affinity | Specific interaction | [169] |
Light scattering | ||
Dynamic light scattering DLS | Size measurements and aggregation study | [170,171] |
Static light scattering | ||
UV-Visible absorbance spectroscopy | Agglomeration assessment and stability | [171,172,173] |
Mass spectrometry | Protein quantification, vaccine potency | [34,174] |
Fluorescence spectroscopy | Protein stability, agglomeration assessment | [89,172] |
Microscopy | ||
Transmission electron microscopy TEM | Structure-guided information and aggregation study | [89,171,172] |
Flow imaging microscopy | Size | [175] |
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Nuwarda, R.F.; Alharbi, A.A.; Kayser, V. An Overview of Influenza Viruses and Vaccines. Vaccines 2021, 9, 1032. https://doi.org/10.3390/vaccines9091032
Nuwarda RF, Alharbi AA, Kayser V. An Overview of Influenza Viruses and Vaccines. Vaccines. 2021; 9(9):1032. https://doi.org/10.3390/vaccines9091032
Chicago/Turabian StyleNuwarda, Rina Fajri, Abdulsalam Abdullah Alharbi, and Veysel Kayser. 2021. "An Overview of Influenza Viruses and Vaccines" Vaccines 9, no. 9: 1032. https://doi.org/10.3390/vaccines9091032
APA StyleNuwarda, R. F., Alharbi, A. A., & Kayser, V. (2021). An Overview of Influenza Viruses and Vaccines. Vaccines, 9(9), 1032. https://doi.org/10.3390/vaccines9091032