Influenza B: Prospects for the Development of Cross-Protective Vaccines
Abstract
:1. Background
2. Epidemiological and Ecological Features of Influenza B Infection
3. Organization of the Influenza B Virion and Genome. Viral Proteins as Cross-Protective Vaccine Targets
4. Conserved Protein Epitopes as Target Antigens for the Development of Broadly Protective Influenza B Vaccines
5. Strategies for Developing Cross-Protective Influenza B Vaccines
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Ethical Approval and Consent to Participate
Conflicts of Interest
Abbreviations
a.a. | amino acid |
Abs | antibodies |
ADCC | antibody-dependent cell-mediated cytotoxicity |
ADCP | antibody-dependent cellular phagocytosis |
BVic | influenza B, Victoria-like lineage |
BYam | influenza B, Yamagata-like lineage |
h | human |
HA | hemagglutinin |
HI | hemagglutinin inhibitor |
HLAs | Human Leucocyte Antigens |
hpi | hours post infection |
FLUAV | influenza A virus |
FLUBV | influenza B virus |
IIV | influenza inactivated vaccine |
IRF | interferon regulation factor |
mAbs | monoclonal antibodies |
MHC | major histocompatibility complex |
m | mouse |
NA | neuraminidase |
PB1 | polymerase basic protein 1 |
RBS | receptor binding site |
TIV | trivalent influenza vaccine |
UIV | universal influenza vaccine |
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mAb (Origin) | Target Protein | Action | References |
---|---|---|---|
CR8033 (h) | HA head, epitopes overlapping receptor binding pocket and surrounding antigenic sites | Blocks viral attachment. Binds and neutralizes both IBV lineages and has neutralizing activity against BYam strains | [78] |
CR8071 (h) | HA head, the vestigial esterase domain at the base of the HA head | Binds to the vestigial esterase domain, neutralizing activity in vitro, intermediate protection in vivo | |
CR9114 (h) | HA stalk, epitope conserved across influenza A and B viruses | Blocks the pH-induced conformational changes in HA and membrane fusion, non-neutralizing in vitro, high protection against diverse IBV in vivo | |
5A7 (h) | C terminus of HA1 in the stalk | Blocks viral attachment and membrane fusion, low relative neutralizing potency | [86] |
46B8 (h IgG1) | HA, vestigial esterase domain at the base of the HA head | Blocks HA-mediated membrane fusion by preventing low pH-induced conformational changes | [87] |
C12G6 (m/h) | HA, conserved epitopes in close proximity to the receptor binding pocket (RBP) | Prevents viral entry, viral egress. Displayed ADCC, neutralizing activity against BYam, BVic viruses. Binds a similar epitope to CR8033, overlapping the receptor binding domain | [82] |
TRL784, TRL799, TRL811, TRL812- TLR813, TRL835, TRL837, TRL841, TRL842, TRL846, TRL856 (h) | HA stalk domain | No neutralizing activity | [80] |
TRL845, TRL847, TRL848, TRL849, TRL854 (h) | HA stalk domain | Neutralizes diverse strains of both IBV lineages | |
KL-BHA-6D12 **, KL-BHA-2C6 *, KL-BHA-2G4 *, KL-BHA-4C10 **, KL-BHA-8G3 ** (m) | HA stalk domain, long alpha-helix | No neutralizing activity in vitro Completely (**) or partially (*) protects against a lethal IBV dose from either lineage, effects through the ADCC, ADCP | [76] |
KL-BHA 8G12 **, KL-BHA-4G12 * (m) | HA stalk domain, outside alpha-helix | ||
KL-BHA-1B5 **, KL-BHA-2H11 ** (m) | Globular head domain | ||
KL-BHA-1D2 **, KL-BHA-2H10 **, KL-BHA-9C6 **, KL-BHA-3A10 **, KL-BHA-3H10 *, KL-BHA-8A5 ** (m) | Globular head domain or conformational epitopes of stalk | ||
R95–1E07, R95–1D05, K77–2D09 K77–2D11 (h) | HA head, epitopes proximal to RBP | Bind and neutralize both IBV lineages and have HI activity. Cross-reactive Abs capable of mediating HI showed the greatest protective effect in vivo | [41] |
R95–1F04, R95–1C01, R95–1E05 (h) | HA head domain | Conferred intermediate protection, characterized by broad IBV recognition, but no HIA activity. Protection mediated by mAb engagement with cellular Fc receptors An absence of neutralizing activity in vitro and provided the weakest protection against experimental challenge Bind Fc receptor | |
W85–3F06, R95–1E03, R95–2A08 | HA stalk domain | ||
W85–1A07, W85–3E10 (h) | Within the vestigial esterase domain at the base of the HA | ||
1F2(m) 1F4(m) | Surface of the NA tetramer, not directly overlapping the NA enzymatic active site | Enhance viral clearance, display ADCC activity | [81] |
3G1(m) | NA, epitope overlaps or adjacent to the enzymatic active site | ||
4B2 (m) | Surface of the NA tetramer, right above both the 1F2 and the 4F11 footprints | Enhances viral clearance, displays ADCC activity | |
4F11 (m) | Surface of the NA tetramer, not directly overlapping the NA enzymatic active site | Enhances viral clearance, displays ADCC activity | |
1086C12, 1086F8, 1092D4, 1092E10, 11122C6 (h) | NA | Inhibits NA enzymatic activity and blocks the release of progeny virions | [79] |
HCA 2 | NA | [88] |
Candidate Vaccine or Target Antigens | Vaccine Platform | Approach | Stage of Development | Developer, Partners | References |
---|---|---|---|---|---|
Multimeric- 001(M-001) | Recombinant protein | Recombinant protein featuring conserved epitopes of M1, NP, HA (FLUAV), and M1, NP (FLUBV) | Clinical trials (Ph III, 2020) | Biond Vax Pharmaceuticals (Israel) | [115,116,117] |
FLU-V | Peptide-based | Construct derived from conserved regions of internal proteins (M1, FLUAV-NP, FLUBV-NP, M2) | Clinical trials (Ph IIb, 2020) | Imutex Pep Tcell (SEEK) (UK), EndFluenza (UK) | [118,119,120] |
BM2SR | M2-deficient single-replication live virus | M2-deficient single-replication vaccine for influenza B virus | Clinical trial (Ph II, 2019) | FluGenInc, USA, The Biomedical Research Institute (CA, USA), University of Tokyo (Japan) | [132] |
Chimeric HA | Chimeric virus | Recombinant HA including head domains (FLUAV H5, H7, or H8) and FLUBV stalk domains | Preclinical (2021) | Icahn School of Medicine at Mount Sinai (USA) | [129] |
Mosaic HA | Recombinant virus | HAs were constructed by replacing four major IBV antigenic sites with the corresponding sequences from different FLUAV HAs (H5, H8, H11, or H13) | Preclinical (2021) | Icahn School of Medicine at Mount Sinai (USA) | [130] |
rNA proteins | Recombinant protein | Influenza B virus NA from Yam88 adjuvanted with 5 µg of poly(I C) | Preclinical (2021) | Icahn School of Medicine at Mount Sinai (USA) | [94] |
rAd/B-NP(Y) and rAd/B-NP(V) | Viral vector | Replication-defective adenoviruses (rAd) encoding the conserved NP epitopes FSPIRITFL (BYam) or FSPIRVTFL (BVic) | Preclinical (2019) | Ewha Womans University, Seoul (South Korea) | [141,149] |
HA2 aa90–105 | Nanoparticle | FLUAV (H1, H3) and FLUBV HA subtype consensus HA290–105 peptides were inserted into loops 1, 2, and 3 of norovirus P protein, respectively. | In development | Jilin University (China) | [121] |
A/NP-rAd B/NP-rAd | Viral vector | Replication-deficient (E1 and E3 deleted) adenovirus-5 (rAd) vectors expressing NP antigens from A/PR/8/34 or B/Ann Arbor/1/86 | In developmentt | Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (USA) | [142] |
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Tsybalova, L.M.; Stepanova, L.A.; Ramsay, E.S.; Vasin, A.V. Influenza B: Prospects for the Development of Cross-Protective Vaccines. Viruses 2022, 14, 1323. https://doi.org/10.3390/v14061323
Tsybalova LM, Stepanova LA, Ramsay ES, Vasin AV. Influenza B: Prospects for the Development of Cross-Protective Vaccines. Viruses. 2022; 14(6):1323. https://doi.org/10.3390/v14061323
Chicago/Turabian StyleTsybalova, Liudmila M., Liudmila A. Stepanova, Edward S. Ramsay, and Andrey V. Vasin. 2022. "Influenza B: Prospects for the Development of Cross-Protective Vaccines" Viruses 14, no. 6: 1323. https://doi.org/10.3390/v14061323